Liu H, Xiao Y, Dai C
… +5 more, Chen K, Xu X, Cai J, Hu X, Guo J
Cell Prolif
· 2025 Oct · PMID 40325491
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Autophagy is an evolutionarily conserved process of cell self-catabolism that provides a minimum level of energy for cellular homeostasis during metabolic stress. In radiotherapy (RT), it has been explicitly explained th...Autophagy is an evolutionarily conserved process of cell self-catabolism that provides a minimum level of energy for cellular homeostasis during metabolic stress. In radiotherapy (RT), it has been explicitly explained that autophagy plays a dual role in tumour control by tuning cellular radiosensitivity. However, the underlying molecular mechanism remains a conundrum. Therefore, it is of utmost importance to gain insight into the molecular mechanisms elaborating the autophagy-mediated radiosensitivity and craft refined RT strategies for different tumours. Distinguishing it from previous reviews in the field, here we discuss the mechanisms of autophagy, especially its pro-survival and growth-suppressing mechanisms via regulation of radiosensitivity. We further outline some frontier RT adjuvant therapies targeting autophagy, in an endeavour to shed some light on the autophagy-mediated pathways to harness radiosensitivity.
Guan D, Chen Z, Zhang Y
… +3 more, Sun W, Li L, Huang X
Cell Prolif
· 2025 Sep · PMID 40325291
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Natural killer (NK) cells are critical regulators of immune processes during early pregnancy, playing a key role in maintaining maternal-foetal immune tolerance and supporting successful implantation. In particular, uter...Natural killer (NK) cells are critical regulators of immune processes during early pregnancy, playing a key role in maintaining maternal-foetal immune tolerance and supporting successful implantation. In particular, uterine NK cells, a specialised subset of NK cells, facilitate trophoblast invasion, spiral artery remodelling and placental establishment. Dysregulation of NK cell activity, however, has been implicated in pregnancy complications, notably recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF). Aberrant NK cell functions, such as heightened cytotoxicity or defective immune signalling, can disrupt the balance between immune tolerance and response, leading to impaired placental development, reduced trophoblast activity and compromised uteroplacental blood flow. This review examines the role of NK cells in early pregnancy, emphasising their contributions to immune modulation and placentation. It also investigates the mechanisms by which NK cell dysfunction contributes to RSA and RIF, and explores therapeutic strategies aimed at restoring NK cell balance to improve pregnancy outcomes. A deeper understanding of NK cell interactions during early pregnancy may provide critical insights into the pathogenesis of pregnancy failure and facilitate targeted immunotherapeutic approaches.
Zhao T, Di J, Kang Y
… +4 more, Zhang H, Yao S, Liu B, Rong L
Cell Prolif
· 2025 Oct · PMID 40320759
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Microglia, considered as the main immune responder, play an important role in regulating neuroinflammation in central nervous system (CNS) disorders. Our previous work found that TREM2 is highly expressed in microglia an...Microglia, considered as the main immune responder, play an important role in regulating neuroinflammation in central nervous system (CNS) disorders. Our previous work found that TREM2 is highly expressed in microglia and is related to their functional state. However, the specific role of TREM2 in spinal cord injury has not yet been explored. To further investigate the potential mechanism of TREM2, we performed single-cell sequencing on wild-type (Wt) and Trem2 mice before and after spinal cord injury. Compared to Wt mice, the lysosome, autophagy and membrane-related pathways are more strongly activated in Trem2 mice, suggesting that TREM2 may exert its effects by influencing lysosomal membranes and autophagy. Mechanistically, we demonstrated that the knockout of Trem2 can reduce the nuclear translocation of TFEB by decreasing the phosphorylation of Syk. Furthermore, we validated that in vitro and in vivo silencing Trem2 can promote autophagy by repairing lysosomal membrane permeabilization. Through immunofluorescence, 3D gait analysis, motor evoked potential experiments, H&E staining and Masson staining, we demonstrated that the increased level of autophagy can rescue more microglia in vivo and promote both functional and histological recovery of spinal cord injury. Collectively, these results not only suggest that microglial lysosomal autophagy is regulated in a TREM2-dependent LMP manner, but also, more importantly, they provide a promising clinical translation strategy based on gene therapy for lysosome-related central nervous system disorders.
Sun Y, Hu X, Huang X
… +5 more, Zhou W, Lan S, Zhang H, Wu G, Lei L
Cell Prolif
· 2025 Oct · PMID 40320363
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Ribosome biogenesis occurs within the nucleolus, with the initial step being the transcription of ribosomal DNA (rDNA). Although rDNA transcription is limited in somatic cells, it is more active in stem cells. Neverthele...Ribosome biogenesis occurs within the nucleolus, with the initial step being the transcription of ribosomal DNA (rDNA). Although rDNA transcription is limited in somatic cells, it is more active in stem cells. Nevertheless, the mechanisms involved in somatic cell reprogramming remain elusive. Both somatic and stem cell nucleoli exhibit a reticular structure. However, under the electron microscope, we identified an intermediate nucleolar state during reprogramming. This state underwent changes characterised by rDNA hypertranscription, resulting in an enlarged nucleolus, enhanced activity of nucleolus organiser regions (NORs), and a transition from the reticular nucleolar type to an intermediate state of reprogramming, whose three liquid phase boundaries are blurred. Our research revealed that Oct4 was directly targeted to the rDNA enhancer region, promoting its hypertranscription and nucleolar enlargement during reprogramming. Using rDNA transcriptional inhibitors, we proved that nucleolar remodelling and subsequent reprogramming are halted by inhibiting rDNA transcription. But why could rDNA transcriptional activity influence reprogramming? Our findings elucidate that the active nucleoli have the capability to release perinucleolar heterochromatin. By joint analysis of Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and RNA-seq, we have characterised the perinucleolar chromatin released by the nucleolus in a reprogramming intermediate state. The released chromatin mainly impacted mesenchymal-to-epithelial transition (MET)-related genes. MET is a stage of silencing of mesenchymal genes, accompanied by the activation of epithelial genes. Concurrently, the morphology of mouse embryonic fibroblast cells (MEFs) transitions from elongated spindle-shaped cells to short roundish forms, exhibiting a propensity to cluster together. MET was considered an early event in reprogramming; our findings suggested that nucleolar remodelling occurred before MET.
Zhou G, Tan J, Zhang P
… +3 more, Zhou Z, Zhang L, Zhang Z
Cell Prolif
· 2025 Jul · PMID 40313038
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Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Despite advancements in gene targeted therapies and immunotherapies, high heterogeneity contributes to limited efficacy and therapeutic resi...Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Despite advancements in gene targeted therapies and immunotherapies, high heterogeneity contributes to limited efficacy and therapeutic resistance. Ubiquitination, a crucial post-translational modification that regulates protein stability and degradation, plays a significant role in cancer pathogenesis by influencing key oncogenic pathways and tumour progression. This review systematically explores the ubiquitin-proteasome system (UPS) and its potential as a therapeutic target for NSCLC. We highlight recent preclinical and clinical studies focusing on ubiquitination-related biomarkers, drug targets and emerging therapies like proteasome inhibitors and Proteolysis-targeting chimeras (PROTACs). By exploring the impact of the UPS on tumour biology, the progression of NSCLC and its response to therapy, we aim to underscore the potential of targeting the ubiquitination-deubiquitination system as a complementary or synergistic approach to existing therapeutic strategies in NSCLC, thereby enhancing patient outcomes and overcoming treatment resistance.
Pan Y, Chen L, Shen J
… +11 more, Hong S, Guan X, Ma X, Tang R, Lu M, Sun F, Shang S, Dai Y, Zhou Z, Zhang S, Yang J
Cell Prolif
· 2025 Jul · PMID 40308074
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GANT61 induced autophagy via the AKT pathway and promoted the accumulation of lipid droplets in both cell lines. The molecular mechanism behind this lipid accumulation appears to involve the mediation of SREBP1. Furtherm...GANT61 induced autophagy via the AKT pathway and promoted the accumulation of lipid droplets in both cell lines. The molecular mechanism behind this lipid accumulation appears to involve the mediation of SREBP1. Furthermore, the combination of GANT61 with CQ/Fatostatin significantly inhibited the proliferation and clonogenicity of SKOV3 and SKOV3PTX cells.
Li J, Luo P, Li Z
… +5 more, Wang Q, Huang X, Wang K, Wang R, Chen R
Cell Prolif
· 2025 Jun · PMID 40300805
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Extrachromosomal circular DNA (eccDNA) has emerged as a critical area of cancer research due to its ubiquitous presence in tumour cells and significant role in tumorigenesis, progression and drug resistance. Recent studi...Extrachromosomal circular DNA (eccDNA) has emerged as a critical area of cancer research due to its ubiquitous presence in tumour cells and significant role in tumorigenesis, progression and drug resistance. Recent studies demonstrate that eccDNA promotes cancer progression by influencing genomic instability, amplifying oncogenes, regulating gene expression and enhancing tumour cell adaptability to adverse conditions. While the precise mechanisms underlying eccDNA formation and its biological functions remain unclear, its potential applications in cancer diagnosis, prognosis and targeted therapy are gaining increasing recognition. This review summarises the latest advancements in eccDNA research, highlighting its potential as both a biomarker and a therapeutic target. Additionally, it emphasises the translational potential of eccDNA in clinical diagnostics and personalised treatment strategies, offering new perspectives for future cancer research and innovative therapies.
Qi W, Liu H, Liu H
… +4 more, Guo Y, Wu L, Bao C, Liu X
Cell Prolif
· 2025 Oct · PMID 40298279
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Surgical resection, radiotherapy and chemotherapy are the primary strategies of treating cancers globally. However, the current treatment methods bring new disease burdens to patients due to postoperative complications a...Surgical resection, radiotherapy and chemotherapy are the primary strategies of treating cancers globally. However, the current treatment methods bring new disease burdens to patients due to postoperative complications and multiple side effects, especially in surface tumours such as oral squamous cell carcinoma (OSCC). In this study, we developed a microwave cold atmospheric plasma (CAP) device in conjunction with tumour microenvironment-responsive nanohydroxyapatite (nHA) for the first time. The synergistic effects of CAP and nHA combined application on OSCC were evaluated in both in vitro and in vivo experiments. The synergistic effects of CAP and pH-responsive NH-nHA on the apoptosis, intracellular reactive oxygen species (ROS) and calcium ion concentration of OSCC cells were investigated in vitro. The synergistic induction of CAP with NH-nHA exhibited optimal tumour-specific inhibitory effects on OSCC. The results revealed that the combined application of CAP with NH-nHA induced apoptosis of tumour cells in vitro and killed 84.0% of tumours in vivo. Mechanistically, CAP enhances extracellular ROS production, while NH-nHA amplifies intracellular calcium ion (Ca) concentrations, synergistically increasing intracellular ROS levels to provoke oxidative stress in OSCC cells, ultimately triggering the mitochondrial apoptosis pathway. In conclusion, the combined utilisation of CAP and NH-nHA presents a promising avenue as a novel, selective, and non-invasive strategy in the management of OSCC.
Lee YH, Lim H, Kim G
… +11 more, Jang G, Kuk MU, Park JH, Yoon JH, Lee YJ, Kim D, So B, Kim M, Kwon HW, Byun Y, Park JT
Cell Prolif
· 2025 Oct · PMID 40289552
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Senescent cells are characterised by increased glycolysis dependence. Normalisation of glycolysis metabolism is essential for senescence amelioration. However, the mechanism of proteins involved in cellular glycolysis me...Senescent cells are characterised by increased glycolysis dependence. Normalisation of glycolysis metabolism is essential for senescence amelioration. However, the mechanism of proteins involved in cellular glycolysis metabolism has not been fully elucidated. Here, we identified a candidate compound, an oxazole analogue (KB2764), that can improve senescence. To elucidate the mechanism of the KB2764, we investigated the interacting proteins. KB2764 interacted with alpha-enolase (ENO1) and pyruvate kinase M (PKM), ultimately allowing PKM to phosphorylate ENO1. KB2764 consequently increased mitochondrial ATP production and reduced reliance on glycolysis. Knockdown of the ENO1 experiment in senescent cells demonstrates that regulation of ENO1 activity is a prerequisite for recovery of mitochondrial function. Furthermore, the action of KB2764 extends its application to extend the lifespan of Caenorhabditis elegans. Taken together, our findings reveal a novel mechanism by which senescence is ameliorated through metabolic reprogramming and mitochondrial functional recovery via KB2764-mediated regulation of ENO1 protein activity.
Wang Y, Zhang L, Liu J
… +3 more, Yang Y, Bi Z, Ouyang J
Cell Prolif
· 2025 Jun · PMID 40288954
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Conditioned medium (CM), obtained by mechanical regulation of the paracrine activity of ADSCs, was fused with acellular adipose matrix (AAM) and methyl cellulose (MC) to synthesize a composite hydrogel which was grafted...Conditioned medium (CM), obtained by mechanical regulation of the paracrine activity of ADSCs, was fused with acellular adipose matrix (AAM) and methyl cellulose (MC) to synthesize a composite hydrogel which was grafted onto nude mice. The composite hydrogel could promote soft tissue regeneration by regulating the level of vascular regeneration and inflammation.
Cell Prolif
· 2025 Jul · PMID 40285592
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Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, imposing a substantial global disease burden. However, its pathogenesis remains incompletely understood, and effective treatment strategies...Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, imposing a substantial global disease burden. However, its pathogenesis remains incompletely understood, and effective treatment strategies are still lacking. Organoid technology, in which stem cells or progenitor cells self-organise into miniature tissue structures under three-dimensional (3D) culture conditions, provides a promising in vitro platform for simulating the pathological microenvironment of OA. This approach can be employed to investigate disease mechanisms, carry out high-throughput drug screening and facilitate personalised therapies. This review summarises joint structure, OA pathogenesis and pathological manifestations, thereby establishing the disease context for the application of organoid technology. It then examines the components of the arthrosis organoid system, specifically addressing cartilage, subchondral bone, synovium, skeletal muscle and ligament organoids. Furthermore, it details various strategies for constructing OA organoids, including considerations of cell selection, pathological classification and fabrication techniques. Notably, this review introduces the concept of intelligent manufacturing of OA organoids by incorporating emerging engineering technologies such as artificial intelligence (AI) into the organoid fabrication process, thereby forming an innovative software and hardware cluster. Lastly, this review discusses the challenges currently facing intelligent OA organoid manufacturing and highlights future directions for this rapidly evolving field. By offering a comprehensive overview of state-of-the-art methodologies and challenges, this review anticipates that intelligent, automated fabrication of OA organoids will expedite fundamental research, drug discovery and personalised translational applications in the orthopaedic field.
Zheng W, Wang X, Chen H
… +8 more, He K, Yan X, Zhang Y, Yang Y, Zhang P, Zhu W, Zhu S, Li H
Cell Prolif
· 2025 Oct · PMID 40277037
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Hepatic ischemia-reperfusion injury (HIRI) substantially influences the prognosis of liver transplant recipients. Although kynurenic acid (KYNA) has been associated with protective effects against ischemia-reperfusion in...Hepatic ischemia-reperfusion injury (HIRI) substantially influences the prognosis of liver transplant recipients. Although kynurenic acid (KYNA) has been associated with protective effects against ischemia-reperfusion injury in various organs, the precise mechanisms underlying its protective role in HIRI are not well elucidated. In this study, a 70% mouse HIRI model and an in vitro hypoxia/reoxygenation model were employed to examine the protective effects of KYNA on HIRI. In this study, we illustrate that KYNA influences the methylation status of the Hippo signalling pathway by enhancing the expression of the fat mass and obesity-associated gene (FTO). Within this pathway, large tumour suppressor kinase 1 (LATS1) is identified as a direct target of FTO. Moreover, the stability of LATS1 mRNA exhibits an inverse correlation with FTO levels and is modulated through its interaction with YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2). The reduction in LATS1 expression facilitated Yes-associated protein (YAP) nuclear translocation, decreased hepatocyte apoptosis, and mitigated HIRI. Clinically, elevated levels of serum KYNA correlate with a diminished severity of liver injury post-transplantation. our work revealed that KYNA possesses significant clinical translational potential for the prevention of HIRI, and further exploration of its underlying mechanisms was conducted.
Bai C, Hua J, Meng D
… +11 more, Xu Y, Zhong B, Liu M, Wang Z, Zhou W, Liu L, Wang H, Liu Y, Li L, Chen X, Li Y
Cell Prolif
· 2025 Nov · PMID 40259435
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Glutaminase-1 (GLS1) has garnered considerable interest as a metabolic target in cancer due to its heightened involvement and activity. However, the precise fate of glutaminolysis catalysed by GLS1 in cancer cells remain...Glutaminase-1 (GLS1) has garnered considerable interest as a metabolic target in cancer due to its heightened involvement and activity. However, the precise fate of glutaminolysis catalysed by GLS1 in cancer cells remains elusive. We found that GLS1 knockout led to significant suppression of cancer cell proliferation, which can be reversed or partially restored by supplementation of glutamate or non-essential amino acids that can be converted into glutamate. The addition of spliceosomal KGA or GAC ameliorates cancer cell growth in vitro and in vivo, providing both simultaneously completely reverse the effect. The primary metabolic fate of glutamate produced through glutaminolysis in cancer cells is mainly used to produce glutathione (GSH) for redox homeostasis, not entering the tricarboxylic acid cycle or synthesising nucleotides. GSH monoethyl ester (GSH-MEE) effectively rescues the inhibition of cancer cell proliferation caused by GLS1 knockout. Deletion of GLS1 results in an elevation of reactive oxygen species (ROS) and malondialdehyde (MDA), a reduction of NADPH/NADP ratio, and an augmented susceptibility of cells to ferroptosis. Glutathione Peroxidase 4 (GPX4) and GPX1 exhibit complementary roles in redox regulation, with GLS1 knockout promoting GPX4 degradation. Pharmacological inhibition of GLS1 synergises with GPX4 inhibitor to suppress tumour growth. Dual targeting of GPX4 and GPX1 presents a potent anti-cancer strategy. This metabolic mechanism facilitates a deeper comprehension of the abnormal glutamine metabolism in cancer cells, establishing a theoretical basis for the potential clinical utilisation of GLS1 inhibitors and presenting novel perspectives for advancing combinatorial therapeutic approaches.
Cell Prolif
· 2025 Sep · PMID 40254698
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This paper discussed the role of AlkB homologue 5 (Alkbh5) in the progression of lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS-induced ALI models were established in Alkbh5 knockout (KO) and knock-in (KI)...This paper discussed the role of AlkB homologue 5 (Alkbh5) in the progression of lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS-induced ALI models were established in Alkbh5 knockout (KO) and knock-in (KI) mice. The m6A levels in lung tissues were analysed using m6A dot assays. The lung injury was analysed by determining ALI-related markers and histological staining. Mouse MLE12 cells were exposed to LPS for in vitro experiments, and the influence of Alkbh5 on cell viability, apoptosis and reactive oxygen species (ROS) production was analysed. RNA-seq analysis was performed to analyse gene changes upon Alkbh5 deficiency. Functions of the Alkbh5-C-C motif chemokine ligand 1 (Ccl1) cascade in ALI were further verified using the Alkbh5 antagonist DDO-2728 and a recombinant protein of Ccl1 (mCcl1). Alkbh5 was upregulated in lung tissues following LPS exposure. Alkbh5 knockout in mice mitigated LPS-induced lung injury, as indicated by reduced serum levels of lung injury markers and reduced immune cell infiltration, fibrosis and apoptosis. Conversely, Alkbh5 overexpression in mice resulted in reverse trends. In vitro, Alkbh5 knockdown in MLE12 cells enhanced cell viability while reducing cell apoptosis and ROS production. Mechanistically, Alkbh5 was found to bind to and destabilise Ccl1 mRNA, leading to increased Treg recruitment. Treatment with DDO-2728 or mCcl1 in mice increased Treg infiltration, thus improving lung tissue pathology and reducing lung injury. This study suggests that Alkbh5 is implicated in ALI progression by reducing Ccl1-mediated Treg recruitment, making it a promising target for ALI management.
Li Z, Zou Y, Niu J
… +6 more, Zhang Y, Yang A, Lin W, Guo J, Wang S, Liu R
Cell Prolif
· 2025 Jun · PMID 40251939
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IMPDH2 is a rate-limiting enzyme in guanine nucleotide biosynthesis. It plays diverse roles in various physiological and pathological processes: nucleotide metabolism, inflammation, immune function, ribosomal stress. Str...IMPDH2 is a rate-limiting enzyme in guanine nucleotide biosynthesis. It plays diverse roles in various physiological and pathological processes: nucleotide metabolism, inflammation, immune function, ribosomal stress. Structural or regulatory alterations in IMPDH2 are linked to significant health issues, and critical relevance in disease progression. We aim to underscore the potential of IMPDH2 as a promising therapeutic target for clinical applications.
Xing J, Yang S, Liang Y
… +5 more, Hu P, Dai B, Li H, Xing Y, Zuo Y
Cell Prolif
· 2025 Dec · PMID 40251810
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The mammalian life cycle initiates with the transition of genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA), which becomes pivotal for development. Nevertheless, understandi...The mammalian life cycle initiates with the transition of genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA), which becomes pivotal for development. Nevertheless, understanding the conservation of genes and transcription factors (TFs) that underlie mammalian ZGA remains limited. Here, we compiled a comprehensive set of ZGA genes from mice, humans, pigs, bovines and goats, including Nr5a2 and TPRX1/2. The identification of 111 homologous genes through comparative analyses was followed by the discovery of a conserved genetic coding region, suggesting potential sequence preferences for ZGA genes. Notably, an interpretable machine learning model based on k-mer core features showed excellent performance in predicting ZGA genes (area under the ROC curve [AUC] > 0.81), revealing abundant and intricate 6-base sequence specific patterns and potential binding TFs, including motifs from NR5A2 and TPRX1/2. Further analysis demonstrated that gene sequence features and epigenetic modification features play equally important roles in regulating ZGA genes. Ultimately, we developed the ZGAExplorer platform to provide an invaluable resource for screening ZGA genes. Our study unravels the sequence determinants of ZGA genes across species through multi-omics data integration and machine learning, yielding insights into ZGA regulatory mechanisms and embryonic developmental arrest.
Yang L, Lai X, Lin F
… +11 more, Shi N, Xu X, Wang H, Li X, Shen D, Qian H, Jin X, Chen J, Huang Z, Duan X, Zhang Q
Cell Prolif
· 2025 Oct · PMID 40251808
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As maternal age increases, the decline in oocyte quality emerges as a critical factor contributing to reduced reproductive capacity, highlighting the urgent need for effective strategies to combat oocyte aging. This stud...As maternal age increases, the decline in oocyte quality emerges as a critical factor contributing to reduced reproductive capacity, highlighting the urgent need for effective strategies to combat oocyte aging. This study investigated the protective effects and underlying mechanisms of Echinacoside (ECH) on aging oocytes. ECH significantly improved cytoskeletal stability and chromosomal integrity, as demonstrated by restored spindle morphology and reinforced F-actin structures, essential for meiotic progression. It also preserved mitochondrial function by restoring membrane potential and dynamics, reducing ROS levels, and downregulating the DNA damage marker γ-H2AX, thereby alleviating oxidative stress and enhancing genomic stability. Furthermore, ECH promoted cellular homeostasis through modulation of lipid metabolism, autophagy and lysosomal function. Transcriptomic analyses identified GJA1 as a pivotal mediator of ECH's effects, validated through molecular docking and bio-layer interferometry. Functional studies showed that inhibiting GJA1 significantly reduced ECH's ability to enhance first polar body extrusion rates, mitochondrial function and antioxidant capacity, validating the critical role of the GJA1/SIRT1 pathway in combating oocyte aging. This study provides novel insights into the mechanisms of oocyte rejuvenation and highlights ECH as a promising therapeutic candidate for addressing age-related reproductive challenges.
Cell Prolif
· 2025 Aug · PMID 40211955
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Membraneless organelles (MLOs) are a type of subcellular compartment structure discovered in eukaryotes in recent years. They are mainly formed through the liquid-liquid phase separation (LLPS) and aggregation of macromo...Membraneless organelles (MLOs) are a type of subcellular compartment structure discovered in eukaryotes in recent years. They are mainly formed through the liquid-liquid phase separation (LLPS) and aggregation of macromolecular substances such as proteins or nucleic acids in cells. When cells are stimulated, they initiate a series of stress responses including gene transcription, RNA metabolism, translation, protein modification and signal transduction to maintain homeostasis. The dysregulation of these cellular processes is a key event in the occurrence and development of cancer. This article provides an overview of the structure and function of membraneless organelles, as well as the mechanisms of phase separation, to summarise the latest research progress on phase separation in tumours. It focuses on the role and molecular mechanism of LLPS in the development of tumours, with the aim of providing new theoretical references for developing drug action targets and innovative treatment strategies.