International Journal of Biological Sciences最新文献

{"title":"FAT1 functions as an oncogenic driver in triple negative breast cancer through AKT pathway-driven effects on the matrisome.","authors":"Panpan Zhao, Yuanyuan Zhang, Yang Yu, Qing Zhang, Xiaoying Liu, Xu Dong Zhang, Song Chen, Charles E de Bock, Rick F Thorne, Yujie Shi","doi":"10.7150/ijbs.104921","DOIUrl":"10.7150/ijbs.104921","url":null,"abstract":"<p><p>FAT1 cadherin exhibits dual tumor suppressor and oncogenic roles across various cancers, but its function in breast cancer remains unclear due to conflicting reports of mutational loss and overexpression. In this study, we demonstrate that FAT1 mRNA and protein levels are reduced during mammary transformation, an effect linked to promoter methylation rather than mutational events. Subtype-specific analysis reveals that high FAT1 expression correlates with poor outcomes in basal-like/triple-negative breast cancer (TNBC), while elevated FAT1 expression in luminal A/estrogen receptor-positive breast cancers is associated with improved patient prognosis. Functional studies in TNBC models using knockdown and overexpression approaches confirm that FAT1 promotes both cell proliferation and motility. High-throughput sequencing and biochemical assessments establish strong links between FAT1 phenotypes and the activation of PI3K-AKT signaling. Additionally, FAT1 manipulation induces significant changes in matrisome-related genes, extracellular matrix components, and integrin switching. Together, these findings define an oncogenic role for FAT1 in TNBC, providing mechanistic insights into how its regulation influences AKT signaling, cell proliferation, and motility.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2201-2222"},"PeriodicalIF":8.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is the Impact of Endothelial-to-Mesenchymal Transition in Solid Tumours: A Qualitative Systematic Review and Quantitative Meta-Analysis.","authors":"Pablo Hernández-Camarero, Belén Toledo, Ana Belén Diaz-Ruano, Aitor González-Titos, María Belén García-Ortega, Macarena Perán","doi":"10.7150/ijbs.107045","DOIUrl":"10.7150/ijbs.107045","url":null,"abstract":"<p><p>Endothelial-to-mesenchymal transition (EndMT) has gained increasing recognition as a crucial mechanism in the progression of solid cancers, influencing tumour heterogeneity, metastasis, and resistance to therapy. However, despite its growing importance, EndMT remains insufficiently studied within the cancer research landscape. In this study, we conduct a systematic review, adhered to the 2020 PRISMA guidelines, of the existing literature on EndMT in solid tumours, examining its functional roles, key biomarkers, underlying mechanisms, experimental models, and potential as a target for therapeutic intervention. Our objective was to identify critical areas where further research is needed. In addition, we performed a meta-analysis to evaluate the variability in the expression of EndMT-related markers and their potential links to patient prognosis. To this aim, literature searches were conducted in major databases including PubMed, Scopus, and Web of Science, covering studies published up to June 2024. The risk of bias of selected articles was evaluated using the OHAT tool, for the <i>in vitro</i> experiments and the SYRCLE tool for studies using animal models. Out of an initial pool of 1,197 articles, 54 studies were selected for data extraction by two independent reviewers. Selected studies were identified according to specific inclusion/exclusion criteria applied through distinct stages like \"title and abstract screening\", \"full text article review\" and \"article bibliography screening\". Our analysis confirms that EndMT is a key contributor to tumour progression and metastasis, but several aspects remain poorly understood, particularly regarding the induction of EndMT in specific cancer types, its role in lymphatic endothelial cells, and its interactions with other stromal elements. We observed substantial heterogeneity in the biomarkers associated with EndMT, as well as variations in the endothelial cell types studied, the functional outcomes, and the molecular mechanisms involved. Our meta-analysis revealed significant variability in the expression of EndMT biomarkers, with notable correlations between changes in the expression of specific genes and patient outcomes, particularly in lung cancer. In conclusion, it is essential for future research to focus on identifying the specific cancer and stromal cell types implicated in EndMT and to standardize endothelial cell models and protocols used for inducing EndMT. Investigating EndMT alongside well-established processes, such as epithelial-to-mesenchymal transition (EMT), and exploring its relationship with cancer-associated fibroblasts (CAFs) may provide valuable insights into its role in tumour biology and its impact on therapy resistance.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2155-2178"},"PeriodicalIF":8.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Regulation of Ferroptosis in Cancer Cells.","authors":"Zilin Ding, Zhiyu Li, Kai Sun, Yi Liu, Zhou Fang, Shengrong Sun, Chenyuan Li, Zhong Wang","doi":"10.7150/ijbs.105446","DOIUrl":"10.7150/ijbs.105446","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent nonapoptotic regulated cell death modality characterized by lethal levels of lipid peroxide accumulation and disrupted antioxidant systems. An increasing number of studies have revealed correlations between ferroptosis and the pathophysiology and treatment of cancer. Given the intricate involvement of mitochondria in ferroptosis, as suggested by previous studies, here, we review advances in understanding the roles of mitochondrial quality control and mitochondrial metabolism (including the roles of the TCA cycle, reactive oxygen species, iron metabolism, and lipid metabolism) in cancer-related ferroptosis and outline the molecular mechanism and clinical translation of mitochondria-related ferroptosis in cancer treatment. with the aim of promoting the precise utilization and prevention of ferroptosis in cancer therapeutics.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2179-2200"},"PeriodicalIF":8.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"eNAMPT/Ac-STAT3/DIRAS2 Axis Promotes Development and Cancer Stemness in Triple-Negative Breast Cancer by Enhancing Cytokine Crosstalk Between Tumor-Associated Macrophages and Cancer Cells.","authors":"Lifen Zhang, Lu Wang, Ziyao Xu, Xingmei Zhang, Shaoyu Guan, Zhe Liu, Shanzhi Gu, Lin Zhao, Weichao Bai, Tian Li, Xinhan Zhao","doi":"10.7150/ijbs.103723","DOIUrl":"10.7150/ijbs.103723","url":null,"abstract":"<p><p>The intricate relationship between tumor-associated macrophages (TAMs) and cancer cells is pivotal for carcinogenesis, with TAMs being integral to the tumor microenvironment (TME). This study explores the novel mechanisms by which TAMs regulate the progression of triple-negative breast cancer (TNBC) within the TME. Using a co-culture system and methodologies such as cytokine arrays, proteomics, and CRISPR-Cas9, we investigated the crosstalk between TAMs and TNBC cells. We found that high levels of CD163⁺ TAMs in TNBC tissues correlate with poor prognosis. TNBC cell-conditioned medium induces macrophage polarization towards the M2 phenotype, enhancing TNBC cell migration, invasion, and stemness through the secretion of extracellular nicotinamide phosphoribosyltransferase (eNAMPT). eNAMPT binding to CCR5 on TNBC cells activates STAT3, leading to the downregulation of the tumor suppressor DIRAS2 and an increase in CCL2, which promotes a macrophage recruitment loop. Intervention at the eNAMPT/CCR5 or CCL2 level disrupts this loop, mitigating TAM-induced effects. Our findings uncover a cytokine communication mechanism between immune and cancer cells, suggesting potential targets for TNBC detection and treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2027-2047"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Cyclin D1 by Novel Biguanide Derivative YB-004 Increases the Sensitivity of Bladder Cancer to Olaparib via Causing G0 / G1 Arrest.","authors":"Di Xiao, Xuetong Chu, Weifan Wang, Mei Peng, Qi Lv, Cangcang Xu, Huaxin Duan, Xiaoping Yang","doi":"10.7150/ijbs.105072","DOIUrl":"10.7150/ijbs.105072","url":null,"abstract":"<p><p>Bladder cancer (BC) is the 10^th most common type of tumor worldwide, and recently approved immunotherapies and FGFR inhibitors have been shown to improve the prognosis of only a very limited subset of BC patients. Thus, the quest for more effective drugs remains an urgent priority for improving the quality of life of more BC patients. Previously, we demonstrated that a novel biguanide <b>YB-004</b> has potent antitumor activity. In this study, we found that the novel biguanide <b>YB-004</b> interrupts the cell cycle by reducing the expression of cyclin D1, causing G0/G1 phase arrest, and suppresses homologous recombination (HR) by inhibiting Rad51, thereby increasing DNA damage and blocking BC cell proliferation. Interestingly, our results further revealed that cell accumulation in the S and G2/M phases is the main reason why HR-proficient BC cells are not sensitive to olaparib, as these phases are conducive to HR activation and DNA repair. Thus, <b>YB-004</b> increased the sensitivity of BC cells to olaparib by reversing the cell cycle changes and HR activation caused by olaparib. Taken together, these findings suggest that the combination of <b>YB-004</b> with olaparib has great potential for the clinical treatment of HR-proficient BC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"1984-1998"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contact Cooling-Induced ELOVL4 Enhances Skin Wound Healing by Promoting the Inflammation-to-Proliferation Phase Transition.","authors":"Siyi Zhou, Zeming Li, Ke Li, Yuanli Ye, Huan Liang, Nian'Ou Wang, Weiwei Liu, Jingwei Jiang, Martin Y M Chiang, Aijun Chen, Xiao Xiang, Mingxing Lei","doi":"10.7150/ijbs.107871","DOIUrl":"10.7150/ijbs.107871","url":null,"abstract":"<p><p>Empirical evidence indicates that the rate of wound healing varies through different seasons, where it is higher in spring and fall but lower in summer and winter, suggesting adequate temperatures may promote wound healing via an unknown mechanism. Here we show that adequate temperature facilitates wound healing by inducing the expression of Elongation of Very Long Chain Fatty Acid Elongase 4 (ELOVL4) that curtails the inflammation phase. Using skin injury and skin organoids models, bulk- and single-cell RNA-sequencing and spatial transcriptomics analysis, and <i>in vivo</i> functional perturbations, we first demonstrate that adjusting skin surface temperature to 20°C by contact cooling markedly increases the rate of wound healing via upregulating ELOVL4 in the injured epidermis. We then reveal docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as the key products of ELOVL4 that independently control wound healing by dampening the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). This chain of physiological events enhances wound healing via its timely exit of the inflammatory phase and entry into the proliferation phase of tissue repair. Our findings highlight the skin's adaptability to different temperatures and link the evolutionarily conserved mechanism of long-chain fatty acid synthesis to wound repair while demonstrating the potential application of contact cooling therapy in wound healing.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2067-2082"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YBX1/CD36 positive feedback loop-mediated lipid accumulation drives metabolic dysfunction-associated steatotic liver disease.","authors":"Qingqing Zhang, Fei Li, Qichao Ge, Yihui Wang, Zhenyang Shen, Yuecheng Guo, Junjun Wang, Hanjing Zhangdi, Jingyi Lu, Jiaqi Gao, Guangwen Chen, Qidi Zhang, Xingpeng Wang, Hui Dong, Lungen Lu","doi":"10.7150/ijbs.105798","DOIUrl":"10.7150/ijbs.105798","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disorder mainly caused by an imbalance in lipid homeostasis. Y-box binding protein 1 (YBX1) participates in multiple pathophysiological processes, including embryonic development, tissue repair, liver disorders, and energy metabolism. The objective of this study is to investigate the mechanisms underlying MASLD and characterize the role of YBX1 in MASLD. A positive correlation between hepatic YBX1 expression and MASLD using single-cell sequencing data and human liver samples was observed. Hepatocyte-specific YBX1 deficiency ameliorates MASLD in a mouse model generated by subjecting <i>YBX1</i>-KO^hep and LOXP mice to a high-fat-cholesterol and high-fructose diet. Subsequently, the role of YBX1 in the hepatic lipid deposit was assessed by using primary hepatocytes and by performing transmission electron microscopy and biological and histological analyses. Mechanistically, the elevated YBX1 expression enhances the CD36 expression and its membrane localization by directly binding to the promoter of CD36. Furthermore, CD36 promotes the expression of YBX1 under lipid stimulation. The YBX1/CD36 positive feedback loop facilitates hepatic lipid accumulation. The up-regulation of CD36 attenuated the reduction of hepatic steatosis mediated by hepatic YBX1 deficiency in MASLD mouse models. These findings suggest that YBX1 is essential for hepatic lipid homeostasis. This study reveals a novel mechanism of liver steatosis and shows that targeting YBX1 may represent a potential approach for MASLD treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2118-2134"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BAP1 Represses Sequential Activation of IRAKs and NF-κB Signaling in Pancreatic Cancer.","authors":"Yuhan Zhao, Xueyi Liang, Ruozheng Wei, Feng Guo, Gengdu Qin, Haixin Yu, Jiaying Liu, Wentao Xia, Shanmiao Gou, Heshui Wu, Yingke Zhou","doi":"10.7150/ijbs.104977","DOIUrl":"10.7150/ijbs.104977","url":null,"abstract":"<p><p>The deubiquitinating enzyme BRCA1 Associated Protein-1 (BAP1) has been reported to be shallowly deleted in a subset of pancreatic ductal adenocarcinomas (PDAC) and is believed to play a significant role in the development of chronic pancreatitis-driven PDAC. However, evidence suggests that BAP1 may also be involved in the progression and metastasis of PDAC, though the underlying mechanism remains unclear. Here, we demonstrate that BAP1 deletion leads to the overactivation of the nuclear factor-κB (NF-κB) signaling in PDAC, thereby promoting the proliferation, migration, and invasion of PDAC models both <i>in vivo</i> and <i>in vitro</i>. Mechanistically, BAP1 inhibits the sequential activation of interleukin-1 receptor-associated kinases (IRAKs) in an enzyme-independent manner. BAP1 binds to IRAK1 and inhibits the interaction between IRAK4 and IRAK1, as well as the IRAK4-mediated initiation of IRAK1 phosphorylation and autophosphorylation. This, in turn, prevents the dissociation of IRAK1 from the Myddosome complex and sequential activation of NF-κB. Based on this, we further identified that dual-target inhibitors of IRAK1/4 exhibited significant inhibitory effects on BAP1-deficient tumors in both <i>in vivo</i> and <i>in vitro</i> PDAC models. Our findings elucidate the mechanism by which BAP1 inhibits the NF-κB signaling and present a promising strategy for the targeted treatment of BAP1-deficient pancreatic cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"1949-1965"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2BP3 promotes the proliferation and cisplatin resistance of bladder cancer by enhancing the mRNA stability of CDK6 in an m6A dependent manner.","authors":"Qiang Song, Wei Wang, Hao Yu, Zijian Zhou, Juntao Zhuang, Jiancheng Lv, Linjing Jiang, Xiao Yang, Qiang Lu, Haiwei Yang","doi":"10.7150/ijbs.103522","DOIUrl":"10.7150/ijbs.103522","url":null,"abstract":"<p><p>Cisplatin-based chemotherapy is a primary treatment for bladder cancer, yet the development of chemoresistance poses a significant therapeutic challenge. Insulin-like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA-binding protein and a key m6A reader that regulates various cancers through m6A-dependent mechanisms. However, its role in chemotherapy resistance in bladder cancer remains unclear. Our in <i>vivo</i> and in <i>vitro</i> experiments identified IGF2BP3 as a key regulator of cisplatin resistance in bladder cancer. We demonstrated that IGF2BP3 enhances the stability of CDK6 mRNA in an m6A-dependent manner, leading to increased CDK6 expression. This, in turn, promoted tumor cell proliferation and resistance to cisplatin chemotherapy. Moreover, we showed that the CDK6 inhibitor palbociclib effectively suppresses the pro-growth and chemoresistant effects induced by IGF2BP3 overexpression. These results suggested that the IGF2BP3/m6A/CDK6 axis plays a pivotal role in bladder cancer progression and chemoresistance, and that targeting this pathway with CDK6 inhibitors such as palbociclib may offer a promising therapeutic strategy for overcoming cisplatin resistance in bladder cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2048-2066"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulated Cell Death in Lenvatinib Resistance of Hepatocellular Carcinoma: from Molecular Mechanisms to Therapeutic Strategies.","authors":"Ronggao Chen, Xin Hu, Yingchen Huang, Yao Jiang, Guanrong Chen, Qiaonan Shan, Xiao Xu, Shusen Zheng","doi":"10.7150/ijbs.107195","DOIUrl":"10.7150/ijbs.107195","url":null,"abstract":"<p><p>Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), has been established as the first-line treatment for advanced hepatocellular carcinoma (HCC) because of its superior efficacy when in comparison with sorafenib. However, the inevitable development of drug resistance is a significant barrier to achieve a curative outcome and negatively impacts the prognosis. Therefore, it is imperative to delve into the mechanisms underlying lenvatinib resistance (LR) and to identify potential strategies for rational combination treatments. Regulated cell death (RCD) refers to the process by which cells undergo demise when the adaptive responses are insufficient to maintain homeostasis, and RCD takes a crucial part in the disease progression and response to therapeutic agents including TKI of cancer. Resisting cell death is one of the fundamental hallmarks and the major reasons contributing to drug resistance in cancer. Particularly, numerous studies have demonstrated that RCD (including apoptosis, autophagy, ferroptosis, cuproptosis and pyroptosis) plays a significant role in the emergence of LR in HCC. This article offers an in-depth review of recent discoveries concerning the mechanisms of LR in relation to RCD and proposes potential strategies to boost the effectiveness of lenvatinib by incorporating RCD modulators.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"2012-2026"},"PeriodicalIF":8.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}