International Journal Of Oncology[JOURNAL]
Sun
200 papers
PDLIM2 acts as a central regulator of ubiquitination, immune signaling, and mitochondrial metabolism in lung cancer suppression (Review).
Chuang TH, Guo JH, Yang JX … +3 more , Tseng JC, Wang HJ, Lai CY
Int J Oncol · 2026 Aug · PMID 42396651 · Full text
Lung cancer is a leading cause of cancer‑related mortality worldwide, which underscores the need to identify novel targets for improving early detection, therapeutic efficacy, and long‑term patient outcomes. PDZ and LIM...
Lung cancer is a leading cause of cancer‑related mortality worldwide, which underscores the need to identify novel targets for improving early detection, therapeutic efficacy, and long‑term patient outcomes. PDZ and LIM domain protein 2 (PDLIM2) is a multifunctional adaptor protein that plays a role in cancer biology, particularly in lung cancer. Although PDLIM2 exerts divergent functions across various cancer types, substantial clinical, genetic, and experimental evidence consistently supports its role as a tumor suppressor in lung cancer. PDLIM2 expression is markedly downregulated in the majority of lung tumors representing various histological subtypes and disease stages, and its loss is strongly associated with poor prognosis. Mechanistically, it functions as an E3 ubiquitin ligase or ubiquitin ligase enhancer to promote the degradation of key transcription factors, including NF‑κB/RelA and STAT3, thereby restraining tumor‑associated inflammation, proliferation, survival, immune evasion, and metabolic reprogramming. PDLIM2 downregulation in lung cancer occurs through coordinated genetic and epigenetic mechanisms, including loss of heterozygosity at chromosome 8p21, promoter hypermethylation, histone deacetylation, and oxidative stress‑driven transcriptional repression. Functionally, the restoration of PDLIM2 suppresses lung tumor growth, enhances chemosensitivity, and promotes antitumor immunity, including response to immune checkpoint inhibitors. In addition, a protumoral mechanism of PDLIM2 downregulation involves mitochondrial dysfunction and accumulation of oncometabolites that lead to the activation of hypoxia inducible factor‑1α signaling. Overall, PDLIM2 is emerging as a biomarker and therapeutic target for lung cancer management.
Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).
Zheng X, Zhang J, Mao C … +8 more , Si Y, Chi C, Xiong T, Gu M, Zhang C, Han H, Li Y, Zhang C
Int J Oncol · 2026 Aug · PMID 42359706 · Full text
Tumor metabolic reprogramming is a hallmark of cancer, supporting adaptation to hostile microenvironments and sustained malignancy. Among these changes, abnormal lactate metabolism is central to tumor progression, immune...
Tumor metabolic reprogramming is a hallmark of cancer, supporting adaptation to hostile microenvironments and sustained malignancy. Among these changes, abnormal lactate metabolism is central to tumor progression, immune evasion and therapy resistance. Lactate, once considered a mere glycolytic byproduct, also acts as a signaling molecule influencing cancer behavior. Epigenetic mechanisms, including DNA/RNA methylation, histone modifications and non‑coding RNAs, serve key roles in regulating lactate metabolism. Notably, lactylation, a novel post‑translational modification, links lactate metabolism with epigenetic control. The present review outlines the molecular basis of lactate dysregulation, its epigenetic control and its biological impact on cancer, and highlights emerging therapeutic strategies targeting lactate metabolism.
Stress‑induced catecholamines attenuate sorafenib efficacy by inhibiting ferroptosis in β2‑adrenergic receptor positive renal cell carcinoma.
Ushijima M, Naito S, Ito H … +10 more , Narisawa T, Ichiyanagi O, Kanno H, Fukuhara H, Takai Y, Yagi M, Yamagishi A, Nishida H, Obara Y, Tsuchiya N
Int J Oncol · 2026 Aug · PMID 42359705 · Full text
Ferroptosis, an iron‑dependent form of non‑apoptotic cell death, is a potential target for cancer therapy. Sorafenib, a molecular targeted agent for renal cell carcinoma (RCC), is involved in ferroptosis induction. Chron...
Ferroptosis, an iron‑dependent form of non‑apoptotic cell death, is a potential target for cancer therapy. Sorafenib, a molecular targeted agent for renal cell carcinoma (RCC), is involved in ferroptosis induction. Chronic stress, mediated by catecholamines via β2‑adrenergic receptors (ADRB2), promotes cancer progression, yet its influence on drug resistance and ferroptosis remains elusive. To investigate ADRB expression in RCC, immunohistochemistry of surgical specimens was performed and assessed ADRB mRNA and protein levels were assessed by RT‑qPCR and western blotting in RCC cell lines. To determine whether β‑adrenergic signaling modulates sorafenib sensitivity, we used ADRB2‑expresing ACHN cells and conducted MTS cell viability assays following β‑adrenergic agonist isoproterenol (ISO) stimulation, ADRB2 knockdown by siRNA, as well as a restraint‑stress mouse model in which catecholamine levels were elevated, bearing ACHN cells or ACHN cells with ADRB2 knockdown by shRNA. To evaluate the involvement of ferroptosis, we applied the ferroptosis inhibitor ferrostatin‑1 (Fer‑1) and inducers erastin and RSL3, and measured cell viability, malondialdehyde and reactive oxygen species. To elucidate the mechanism underlying the ISO effect on ferroptosis, MAPK pathway activity was assessed by western blotting and MTS assays performed under MAPK inhibition. The present study confirmed ADRB2 expression in RCC by immunohistochemistry of surgical specimens. Using the ADRB2‑expressing RCC cell line ACHN, the present study demonstrated that stimulation with the β‑adrenergic agonist isoproterenol (ISO) conferred resistance to sorafenib both and in a mouse stress model; this effect was abrogated by ADRB2 knockdown. Similarly to ISO, Fer‑1 diminished sorafenib sensitivity in ACHN cells. Erastin and RSL3 markedly decreased cell viability, however, ISO attenuated ferroptosis in ACHN cells. Mechanistically, ISO inhibited the phosphorylation of ERK1/2, p38 and JNK, all of which contribute to ferroptosis suppression. These findings provide evidence that chronic stress‑induced ADRB2 activation promotes sorafenib resistance by mitigating ferroptotic cell death.
[Expression of Concern] TIP60 governs the auto‑ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex.
Ahmad T, Ashraf W, Ibrahim A … +6 more , Zaayter L, Muller CD, Hamiche A, Mély Y, Bronner C, Mousli M
Int J Oncol · 2026 Aug · PMID 42359702 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blots shown in Fig. 5A on p. 9 for the experiments without MG132 treatment ('‑ MMGM132'...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blots shown in Fig. 5A on p. 9 for the experiments without MG132 treatment ('‑ MMGM132') were strikingly similar to the GAPDH control western blots shown in Fig. 5D, albeit with some horizontal and vertical resizing of the bands. In addition, an independent analysis of the data in this paper revealed that the flow cytometric plots for the TIP60‑transfected cells experiment in Fig. 8B on p. 12 were also strikingly similar to the plots shown to represent the TIP60‑eGFP Positive cells experiment in Fig. 8E. The authors have been contacted by the Editorial Office to offer an explanation for the apparent re‑use of the abovementioned data in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 59: 89, 2021; DOI: 10.3892/ijo.2021.5269].
Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).
Zhang D, Zhang Y, Liu F … +2 more , Zhang C, Jiang S
Int J Oncol · 2026 Aug · PMID 42359694 · Full text
Glioblastoma (GBM) is currently the most lethal type of primary brain tumor, with a median survival time of 15‑20 months despite the use of multimodal therapy. Although radiotherapy (RT) remains a cornerstone of GBM trea...
Glioblastoma (GBM) is currently the most lethal type of primary brain tumor, with a median survival time of 15‑20 months despite the use of multimodal therapy. Although radiotherapy (RT) remains a cornerstone of GBM treatment, a subset of patients who initially respond to RT eventually acquire resistance, leading to tumor relapse. The emergence of radioresistance severely impairs the long‑term efficacy of RT, highlighting the importance of understanding its underlying mechanisms. The present review synthesizes emerging evidence that therapy‑induced remodeling of the blood‑brain barrier (BBB), upregulation of ATP‑binding cassette efflux transporters, hypoxia‑driven hypoxia inducible factor‑1α signaling and tumor microtube (TM)‑mediated intercellular communication converge to create a self‑reinforcing resistance network. These interconnected mechanisms collectively drive adaptive radioresistance, rather than acting in isolation. Based on this framework, the present review evaluates therapeutic strategies designed to disrupt distinct nodes of this network, including epigenetic modulators, poly (ADP‑ribose) polymerase inhibitors, BBB‑penetrant agents and TM‑targeting approaches, such as connexin43 peptide inhibitors and high‑linear energy transfer particle therapy. The clinical implications of these findings are discussed, with emphasis on biomarker‑driven patient stratification and combinatorial regimens that concurrently target multiple resistance mechanisms.
[Retracted] Honokiol, a phytochemical from , inhibits breast cancer cell migration by targeting nitric oxide and cyclooxygenase‑2.
Singh T, Katiyar SK
Int J Oncol · 2026 Aug · PMID 42359677 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the cell migration assay data shown in Fig. 2A on p. 772, the 'Honokiol Conc. 10 M' data panels relating to...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the cell migration assay data shown in Fig. 2A on p. 772, the 'Honokiol Conc. 10 M' data panels relating to the 4T1 and MCF‑7 cell lines contained an overlapping section, such that data which were intended to show the results from experiments performed in different cell lines had been derived from the same original source. In addition, the western blot data featured in Fig. 4A were published at around the same time in a couple of papers in different journals that featured the same authors, wherein the experiments reported were conducted differently compared with the experimental conditions reported in the above paper; both of these papers have subsequently been retracted. Given the re‑use of data that has been identified in the above paper, together with the apparently incorrect assembly of the data in Fig. 2A, the Editor of has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply.The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 38: 769‑776, 2011; DOI: 10.3892/ijo.2011.899].
Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).
Tao Z, Zhou Z, Wu Y … +1 more , Hu J
Int J Oncol · 2026 Aug · PMID 42318956 · Full text
Cancer‑associated fibroblasts (CAFs) in the tumor microenvironment (TME) are involved in tumor pathogenesis. Fibroblast activation protein (FAP) CAFs are the predominant CAF subtype across multiple cancer types, includin...
Cancer‑associated fibroblasts (CAFs) in the tumor microenvironment (TME) are involved in tumor pathogenesis. Fibroblast activation protein (FAP) CAFs are the predominant CAF subtype across multiple cancer types, including breast, lung and pancreatic cancer. FAP CAFs are crucial contributors to tumor progression. However, incomplete understanding of the biology of FAP CAFs limits their potential for clinical application. The present review aimed to summarize the characteristic features, functions and underlying mechanisms of FAP CAFs in tumor growth, including their involvement in extracellular matrix organization, tumor expansion and immunomodulation within the TME, in which FAP plays an important role, and FAP CAF‑based strategies for tumor diagnosis and therapeutic intervention. The present study aimed to provide a conceptual framework for the multifaceted roles of FAP CAFs in cancer progression to guide development of optimized FAP CAF‑targeted diagnostics and therapies.
[Retracted] Downregulation of uPA/uPAR inhibits intermittent hypoxia‑induced epithelial‑mesenchymal transition (EMT) in DAOY and D283 medulloblastoma cells.
Gupta R, Chetty C, Bhoopathi P … +4 more , Lakka S, Mohanam S, Rao AS, Dinh DH
Int J Oncol · 2026 Aug · PMID 42272242 · Full text
Following the publication of the above article, a concerned reader drew to the Editor's attention that there were anomalies associated with the cellular images shown in Fig. 1A; essentially, groupings of cells/cellular f...
Following the publication of the above article, a concerned reader drew to the Editor's attention that there were anomalies associated with the cellular images shown in Fig. 1A; essentially, groupings of cells/cellular features appeared to be strikingly similar in appearance, looking internally within four of the eight data panels in this figure. A similar phenomenon of strikingly similar features was observed in the majority of the panels showing spheroid formation assay data in Fig. 8A. Moreover, regarding the western blots shown in Fig. 2B for the D283 cell line, the protein bands shown for E‑cadherin for the normoxia and hypoxia cells [the (N) lanes] were strikingly similar, suggesting that the gels in this figure may have featured inappropriate editing. Finally, some of the western blot data featured in Fig. 5C were very similar to data that had appeared in a paper by the same authors published in the journal PLoS One. After having conducted an internal investigation of the data in this paper, the Editor of has decided that this article should be retracted from the journal on the grounds of a lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply.The Editor sincerely apologizes to the readership for any inconvenience caused, and we thank the reader for bringing this matter to our attention. [International Journal of Oncology 733‑744, 2011; DOI: 10.3892/ijo.2010.883].
Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).
Zhang L, Shen D, Feng J … +1 more , Tang L
Int J Oncol · 2026 Aug · PMID 42246190 · Full text
Over half of patients with melanoma exhibit v‑Raf murine sarcoma viral oncogene homolog B (BRAF) mutations, which drive hyperactivation of the MAPK pathway and confer high proliferative potential. To target this oncogeni...
Over half of patients with melanoma exhibit v‑Raf murine sarcoma viral oncogene homolog B (BRAF) mutations, which drive hyperactivation of the MAPK pathway and confer high proliferative potential. To target this oncogenic mutation, BRAF inhibitors, as well as MEK inhibitors (targeting the downstream effector of BRAF), have been approved for melanoma therapy. Although these inhibitors initially decrease the tumor burden, nearly all patients eventually develop drug resistance, leading to aggressive disease relapse at both the primary and metastatic sites. Understanding the mechanisms underlying tumor escape from drug lethality is crucial for the development of strategies against melanoma. The present study aimed to summarize the discovery, development and clinical evolution of the BRAF and MEK inhibitors approved for the treatment of melanoma, their notable efficacy in suppressing aggressive melanoma progression and the underlying mechanisms of acquired resistance.
Metabolic remodeling by circular RNAs in gastric tumorigenesis: From mechanisms to biomarker discovery (Review).
Liang X, Wang T, Ma J … +5 more , Zhao S, Gao W, Yang Y, Zhang X, Li H
Int J Oncol · 2026 Jul · PMID 42246184 · Full text
Gastric cancer (GC), which primarily originates from gastric mucosal epithelium, is driven by factors such as infection, genetic susceptibility and lifestyle. GC poses a serious threat to patient survival and quality of...
Gastric cancer (GC), which primarily originates from gastric mucosal epithelium, is driven by factors such as infection, genetic susceptibility and lifestyle. GC poses a serious threat to patient survival and quality of life. Metabolic reprogramming, a hallmark of tumorigenesis and progression, enables cancer cells to continuously adapt their energy metabolism to support proliferation, invasion, metastasis and drug resistance. Circular RNAs (circRNAs) are a class of non‑coding RNAs characterized by a covalently closed circular structure, which confers high stability. They are differentially expressed in tumor cells and facilitate tumor proliferation and metastasis through multiple mechanisms such as microRNA sponging, protein binding, short peptide translation and N‑methyladenosine modification. Furthermore, circRNAs contribute to tumor metabolic remodeling, meeting the energy demands of tumor cells by regulating key enzymes and transporters involved in metabolic pathways, thereby modulating the synthesis or degradation of metabolites. The present review summarizes the mechanisms by which circRNAs mediate different metabolic modes during the initiation and progression of GC as well as discusses their potential as biomarkers for GC. By systematically elucidating the intricate interactions between circRNAs and metabolic reprogramming in GC, the present study aims to provide a theoretical foundation for the development of innovative therapeutic strategies against GC.
Emerging agents that target signaling pathways in cancer fibroblast cells (Review).
Wan Y, Liu XQ, Liu D … +2 more , Li KD, Zhang DD
Int J Oncol · 2026 Jul · PMID 42246174 · Full text
Cancer‑associated fibroblasts (CAFs) play a critical role in cancer development, recurrence and metastasis. Several signaling pathways are crucial in CAF development, including fibroblast activation protein (FAP), phosph...
Cancer‑associated fibroblasts (CAFs) play a critical role in cancer development, recurrence and metastasis. Several signaling pathways are crucial in CAF development, including fibroblast activation protein (FAP), phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), Janus kinase/signal transducers and activators of transcription (JAK/STAT), nuclear factor κB (NF‑κB), transforming growth factor β (TGF‑β), ferroptosis, apoptosis and autophagy pathways. Targeting the ferroptosis signaling pathway specifically kills CAFs. Therefore, targeting these pathways may inhibit the protumorigenic functions of CAFs. Small molecule drugs, due to their well‑dispersed spatial structures and distinct chemical properties, exhibit promising druggability and pharmacokinetic profiles. These characteristics make small molecule drugs highly advantageous in drug development and increasingly favored in the market. The present review summarized current studies on small molecule compounds that inhibit CAF progression, encompassing inhibitors of the PI3K/AKT/mTOR, JAK/STAT, TGF‑β and NF‑κB pathways, as well as activators of the FAP, ferroptosis, apoptosis and autophagy pathways. These small molecule compounds underscore the significance of CAFs in tumor progression and suggest novel strategies for cancer treatment by targeting CAFs in clinical settings.
[Corrigendum] Cell density‑dependent regulation of p73 in breast cancer cells.
Tophkhane C, Yang S, Zhao ZJ … +1 more , Yang X
Int J Oncol · 2026 Jul · PMID 42212371 · Full text
Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the control β‑actin blots shown for the western blots portrayed in Figs. 1B and 2B were strikingly similar af...
Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the control β‑actin blots shown for the western blots portrayed in Figs. 1B and 2B were strikingly similar after a slight adjustment was made to one set of the bands, even though the experiments shown for the p73β protein were different in these figure parts. After re‑examining their original data, the authors have realized that the β‑actin blots correctly shown for Fig. 2B had inadvertently been included in Fig. 1B. The revised version of Fig. 1, now showing the β‑actin blots that were correctly associated with Fig. 1B, is shown opposite. The authors are grateful to the Editor of for allowing them this opportunity to publish a Corrigendum, and all the authors agree to its publication. Note that this error did not grossly affect either the results or the conclusions reported in this study; furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 35: 1429‑1434, 2009; DOI: 10.3892/ijo_00000461].
P2X7 receptor: An emerging therapeutic target in acute myeloid leukemia (Review).
Liu Y, Xue H, Mai H … +4 more , Sang T, Li Z, Wang N, Feng L
Int J Oncol · 2026 Jul · PMID 42212355 · Full text
The P2X7 receptor (P2X7R) is a ligand‑gated ion channel that exhibits bifunctional properties, switching between a cation‑permeable channel and a large cytolytic pore. In acute myeloid leukemia (AML), P2X7R is aberrantly...
The P2X7 receptor (P2X7R) is a ligand‑gated ion channel that exhibits bifunctional properties, switching between a cation‑permeable channel and a large cytolytic pore. In acute myeloid leukemia (AML), P2X7R is aberrantly overexpressed, particularly in leukemia stem cells (LSCs) and AML blasts. Within the bone marrow niche of AML, P2X7R binding by extracellular adenosine triphosphate not only contributes to a profound immunosuppressive niche that protects the AML cells from immune surveillance, but also drives LSC proliferation, survival, homing, and self‑renewal through downstream signaling cascades, including the cAMP response element‑binding protein/phosphoglycerate dehydrogenase/serine metabolic axis, PBX homeobox 3, Wnt/β‑catenin, and c‑Myc. Elevated P2X7R expression is associated with poor prognosis, chemoresistance, and disease recurrence of AML. The central role of P2X7R in AML pathophysiology makes it a potential biomarker for prognostic stratification and a promising therapeutic target. Several targeting strategies are currently under investigation, including the small molecule antagonists and specific anti‑P2X7R antibodies. Furthermore, a therapeutic approach involves combining P2X7R inhibition with conventional chemotherapy. In conclusion, targeting the P2X7R pathway represents a potential novel and multi‑faceted strategy to improve outcomes for patients with AML by remodeling its protective microenvironment and directly attacking the leukemia cells.
[Expression of Concern] Histone deacetylase inhibitors induce in human hepatoma HepG2 cells acetylation of p53 and histones in correlation with apoptotic effects.
Carlisi D, Vassallo B, Lauricella M … +6 more , Emanuele S, D'anneo A, Di Leonardo E, Di Fazio P, Vento R, Tesoriere G
Int J Oncol · 2026 Jul · PMID 42169657 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the western blot analyses shown in Fig. 2A and B on p. 179, the control β‑actin blots in Fig. 2A...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the western blot analyses shown in Fig. 2A and B on p. 179, the control β‑actin blots in Fig. 2A were very similar to a section of the control blots in Fig. 2B, albeit with some horizontal and vertical resizing of the bands in question, even though the affected lanes of the gel highlighted different experimental treatments. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 32: 177‑184, 2008; DOI: 10.3892/ijo.32.1.177].
[Retracted] Semaphorin 5A suppresses the proliferation and migration of lung adenocarcinoma cells.
Ko PH, Lenka G, Chen YA … +4 more , Chuang EY, Tsai MH, Sher YP, Lai LC
Int J Oncol · 2026 Jul · PMID 42169646 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that Fig. 1, showing that the downregulation of SEMA5A in lung adenocarcinoma tissues is associated with poor ove...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that Fig. 1, showing that the downregulation of SEMA5A in lung adenocarcinoma tissues is associated with poor overall survival, was strikingly similar to a figure that had previously appeared in an article by Dan Wang and colleagues in in 2014 (doi: 10.18081/2333‑5106/014‑03/292‑305). Upon receiving notification of this issue, the authors identified that Fig. 1, as shown, had been included in this paper erroneously, and requested that a corrigendum be published, featuring the correct data for Fig. 1. However, after carefully considering the matter, the Editor of has decided that this paper should instead be retracted from the Journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 56: 165‑177, 2020; DOI: 10.3892/ijo.2019.4932].
Integrin beta 4 promotes colorectal cancer progression by upregulating Ezrin and activating the Wnt/β‑catenin signaling pathway.
Wang J, Si Y, Xuan M … +8 more , Han S, Liu K, Jiao J, Men X, Li H, Wang J, Liu T, Yu W
Int J Oncol · 2026 Jul · PMID 42169639 · Full text
Colorectal cancer (CRC) is a major cause of cancer‑related mortality worldwide. Integrin beta 4 (ITGB4) has been previously identified as being overexpressed in CRC; however, its precise oncogenic mechanism remains uncle...
Colorectal cancer (CRC) is a major cause of cancer‑related mortality worldwide. Integrin beta 4 (ITGB4) has been previously identified as being overexpressed in CRC; however, its precise oncogenic mechanism remains unclear. The present study aimed to elucidate the functional role of ITGB4 in CRC progression and identify its downstream molecular effectors to provide new insights for targeted therapy. The biological functions of ITGB4 were investigated in CRC cell lines (SW480 and HCT116) using a series of assays, including Cell Counting Kit‑8, colony formation, Transwell migration and invasion, and flow cytometry for apoptosis following ITGB4 knockdown. An xenograft mouse model was used to evaluate the effect of ITGB4 on tumor growth. Downstream targets were screened using RNA sequencing (RNA‑seq) and validated by co‑immunoprecipitation and co‑immunofluorescence. The underlying signaling pathway was investigated by western blotting and functional rescue experiments. The results demonstrated that knockdown of ITGB4 significantly suppressed CRC cell proliferation, migration and invasion, while promoting apoptosis . Similarly, silencing ITGB4 markedly inhibited tumor growth in the xenograft model. RNA‑seq analysis identified Ezrin (EZR) as a key downstream target of ITGB4, and a direct protein‑protein interaction was confirmed between them. Mechanistically, ITGB4 knockdown decreased the expression of EZR at both the mRNA and protein levels. ITGB4 was demonstrated to exert its pro‑tumorigenic effects through the regulation of EZR, which subsequently activated the Wnt/β‑catenin signaling pathway. Interestingly, EZR overexpression partially restored ITGB4 levels, suggesting a hypothetical positive feedback loop via Wnt/β‑catenin signaling that could amplify this oncogenic axis. Notably, the malignant phenotypes suppressed by ITGB4 silencing were significantly rescued by the overexpression of EZR. In conclusion, the present study identified a novel ITGB4/EZR/Wnt/β‑catenin signaling axis in CRC. ITGB4 promotes CRC progression by modulating EZR expression and subsequently activating the Wnt/β‑catenin pathway. These findings highlight ITGB4 as a potential prognostic biomarker and a promising therapeutic target for CRC.
Deubiquitinating enzymes in cervical cancer: Molecular mechanisms and therapeutic implications (Review).
Pei CZ, Song XX, Xu H … +1 more , Baek KH
Int J Oncol · 2026 Jul · PMID 42138186 · Full text
Cervical cancer (CC) remains a major global gynecological malignancy, with a rising incidence among younger women in specific regions. Human papillomavirus (HPV) screening and cytological examination have markedly reduce...
Cervical cancer (CC) remains a major global gynecological malignancy, with a rising incidence among younger women in specific regions. Human papillomavirus (HPV) screening and cytological examination have markedly reduced the disease burden; nonetheless, tumor progression, therapeutic resistance and recurrence continue to pose major clinical challenges. Thus, elucidating the molecular mechanisms underlying the progression of CC is crucial. Deubiquitinating enzymes (DUBs) regulate ubiquitin‑dependent protein turnover and signaling, emerging as vital modulators of cell cycle progression, DNA damage response, apoptosis, immune regulation and HPV‑associated carcinogenesis. Notably, DUBs facilitate CC progression by stabilizing oncogenic proteins, regulating tumor suppressors and modulating major signaling pathways. In addition, several DUBs are closely associated with radiosensitivity, chemoresistance and potential targeted therapeutic strategies. The present review summarizes the molecular mechanisms and therapeutic implications of DUBs in CC, while discussing their translational value for future clinical applications.
[Retracted] Radiation‑inducible silencing of uPA and uPAR and in meningioma.
Gogineni VR, Nalla AK, Gupta R … +4 more , Gorantla B, Gujrati M, Dinh DH, Rao JS
Int J Oncol · 2026 Jul · PMID 42138185 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the immunocytochemical and immunohistochemical experiments shown in Fig. 5A‑C on p. 815, several of the...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the immunocytochemical and immunohistochemical experiments shown in Fig. 5A‑C on p. 815, several of the data panels exhibited overlapping sections, such that the data shown in the affected panels had all apparently been derived from the same original sources. Owing to the large number of duplications of data that were identified in this paper, the Editor of has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 36: 809‑816, 2010; DOI: 10.3892/ijo_00000557].
BMP4 derived from human gastrointestinal carcinoma cells impairs myogenic differentiation: A possible mechanism of cancer‑induced cachexia.
Higure K, Kitajima Y, Kimura N … +4 more , Ikeda S, Matsufuji S, Tanaka T, Noshiro H
Int J Oncol · 2026 Jul · PMID 42138180 · Full text
Gastrointestinal cancer (GIC) frequently causes cancer cachexia, the major feature of which is the loss of skeletal muscle mass. The degradation of muscular proteins by cancer‑derived factors in the major pathogenesis of...
Gastrointestinal cancer (GIC) frequently causes cancer cachexia, the major feature of which is the loss of skeletal muscle mass. The degradation of muscular proteins by cancer‑derived factors in the major pathogenesis of cancer‑induced muscle wasting is a known phenomenon. However, this mechanism has mainly been demonstrated using rodent cancer cells, and it may not always be applicable to human cancer types. Impaired skeletal muscle differentiation and regeneration have attracted attention as alternative inducers of cancer cachexia. The present study revealed that conditioned medium from four human GIC cell lines inhibited C2C12 myoblast differentiation by inducing the expression of the inhibitor of DNA binding (Id) proteins Id1 and Id3, which mediated via bone morphogenetic protein (BMP)‑Smad signaling. The results suggested that BMP‑Smad1/5/8‑Id signaling inhibited the expression of a MRF member, myogenin and its downstream myogenic genes, thus leading to unsuccessful differentiation into myotubes. Furthermore, the present study identified high levels of BMP4 secretion from these four human GIC cell lines and demonstrated that an inhibitor of BMP receptor, dorsomorphin or abrogation of BMP4 by siRNA in the GIC cells restored myogenic differentiation in C2C12 cells. The present study uncovered, for the first time, that BMP4 derived from human GIC cells exogenously inhibited myoblast differentiation by activating the Smad1/5/8‑Id signaling axis. In the future, this study may help to elucidate the complicated mechanisms underlying cancer‑induced cachexia in humans.
snoRNAs and their derived sdRNAs: Emerging regulators, biomarkers, and therapeutic targets in human cancers (Review).
Mao J, Lin H, Gu F … +1 more , Pan Z
Int J Oncol · 2026 Jul · PMID 42138179 · Full text
Small nucleolar RNAs (snoRNAs) are a conserved class of non‑coding RNAs that guide 2'‑O‑methylation and pseudouridylation of ribosomal RNA. First identified over five decades ago, snoRNAs have emerged as critical regulat...
Small nucleolar RNAs (snoRNAs) are a conserved class of non‑coding RNAs that guide 2'‑O‑methylation and pseudouridylation of ribosomal RNA. First identified over five decades ago, snoRNAs have emerged as critical regulators of cellular function, with high‑throughput sequencing revealing their dysregulation in numerous human diseases, particularly cancer. In the present review, the biogenesis, classification, and modification mechanisms of snoRNAs and snoRNA‑derived fragments (sdRNAs) are comprehensively summarized. Recent advances in understanding their non‑canonical functions are highlighted, which extend beyond ribosomal RNA modification to include regulation of mRNA splicing, stability, and protein interactions. These diverse mechanisms enable snoRNAs to influence key cancer‑related processes such as proliferation, metastasis, metabolic reprogramming, and therapy resistance. A comprehensive overview of snoRNA dysregulation across major cancer types is provided, including colorectal, hepatocellular, gastric, lung, breast, and ovarian cancers, with a detailed discussion of underlying molecular pathways. Furthermore, their emerging potential as diagnostic and prognostic biomarkers detectable in liquid biopsies is examined, as well as their promise as therapeutic targets amenable to antisense oligonucleotide and small molecule intervention. The present review integrates current knowledge of snoRNA/sdRNA biology and highlights critical gaps and future directions, providing a foundation for translating these regulatory RNAs into clinical oncology applications.
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