Cell Communication and Signaling最新文献

{"title":"Combination therapy with Chicoric acid and PD-1/PD-L1 blockade improves the immunotherapy response in patient-derived ovarian cancer xenograft model.","authors":"Hongwei Lan, Jingjuan Zhu, Helei Hou, Chuantao Zhang, Xingfa Huo, Yuming Zhang, Fangfang Yang, Na Zhou, Xiaochun Zhang","doi":"10.1186/s12964-025-02146-7","DOIUrl":"10.1186/s12964-025-02146-7","url":null,"abstract":"<p><strong>Purpose: </strong>Limited treatment options exist for refractory ovarian cancer (OC) due to its poor response to immune therapies. Therefore, there is an urgent need to develop new effective treatment strategies. Chicoric acid (CA) is reported to have immune-enhancing properties, but its efficacy in cancer treatment is not well understood. We hypothesize that CA might improve the efficacy of PD-1/PD-L1 blockade immunotherapy in refractory OC patients.</p><p><strong>Methods: </strong>Patient-derived xenograft (PDX) models were constructed from chemoresistant advanced high-grade serous ovarian cancer patients. These models were treated with CA, aPD-1/aPD-L1 antibodies, or a combination of both. Single-cell RNA sequencing was performed to analyze the cellular composition of the tumor microenvironment (TME), evaluate treatment efficacy, and explore therapeutic mechanisms. Variations in peripheral blood lymphocytes were analyzed via fluorescence-activated cell sorting. Immunohistochemistry confirmed the variations in tumor-infiltrating lymphocytes and tumor cells.</p><p><strong>Results: </strong>Immunocompetent peripheral blood mononuclear cell (PBMC)-PDX models were successfully constructed using malignant ascites fluid and PBMCs. After treatment, 158,734 cells from 15 samples were categorized into epithelial cells, T lymphocytes, myeloid cells, fibroblasts, and endothelial cells. CA enhanced the antitumor ability of immune cells against OC cells. Notably, CA stimulated the proliferation of CD45 + and CD3 + cells and promoted the migration of CD8 + and CD4 + T cells from peripheral blood to infiltrate the TME. Additionally, CA enhanced the response of OCs to aPD-L1/aPD-1 treatment, strengthened the interaction between tumor and nontumor cells, and identified APP/CD74 as a critical ligand‒receptor pair. CHI3L1 was also found to be a potential marker for predicting immunotherapy efficacy in OC.</p><p><strong>Conclusion: </strong>This study demonstrated that combination therapy with CA and aPD-1/aPD-L1 might be a promising strategy for treating OC effectively.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"137"},"PeriodicalIF":8.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634989","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":"Phosphoproteomics identifies determinants of PAK inhibitor sensitivity in leukaemia cells.","authors":"Pedro Casado, Santiago Marfa, Marym M Hadi, Henry Gerdes, Sandra M Martin-Guerrero, Farideh Miraki-Moud, Vinothini Rajeeve, Pedro R Cutillas","doi":"10.1186/s12964-025-02107-0","DOIUrl":"10.1186/s12964-025-02107-0","url":null,"abstract":"<p><strong>Background: </strong>The P21 activated kinases (PAK) are frequently dysregulated in cancer and have central roles in oncogenic signalling, prompting the development of PAK inhibitors (PAKi) as anticancer agents. However, such compounds have not reached clinical use because, at least partially, there is a limited mechanistic understanding of their mode of action. Here, we aimed to characterize functional and molecular responses to PAKi (PF-3758309, FRAX-486 and IPA-3) in multiple acute myeloid leukaemia (AML) models to gain insights on the biochemical pathways affected by these inhibitors in this disease and identify determinants of response in patient samples.</p><p><strong>Methods: </strong>We mined phosphoproteomic datasets of primary AML, and used proteomics and phosphoproteomics to profile PAKi impact in immortalized (P31/Fuj and MV4-11), and primary AML cells from 8 AML patients. These omics datasets were integrated with gene dependency data to identify which proteins targeted by PAKi are necessary for the proliferation of AML. We studied the effect PAKi on cell cycle progression, proliferation, differentiation and apoptosis. Finally, we used phosphoproteomics data as input for machine learning models that predicted ex vivo response in two independent datasets of primary AML cells (with 36 and 50 cases, respectively) to PF-3758309 and identify markers of response.</p><p><strong>Results: </strong>We found that PAK1 activation- measured from phosphoproteomics data- was predictive of poor prognosis in primary AML cases. PF-3758309 was the most effective PAKi in reducing proliferation and inducing apoptosis in AML cell lines. In cell lines and primary cells, PF-3758309 inhibited PAK, AMPK and PKCA activities, reduced c-MYC transcriptional activity and the expression of ribosomal proteins, and targeted the FLT3 pathway in FLT3-ITD mutated cells. In primary cells, PF-3758309 reduced STAT5 phosphorylation at Tyr699. Functionally, PF-3758309 reduced cell-growth, induced apoptosis, blocked cell cycle progression and promoted differentiation in a model-dependent manner. ML modelling accurately classified primary AML samples as sensitive or resistant to PF-3758309 ex vivo treatment, and highlighted PHF2 phosphorylation at Ser705 as a robust response biomarker.</p><p><strong>Conclusions: </strong>In summary, our data define the proteomic, molecular and functional responses of primary and immortalised AML cells to PF-3758309 and suggest a route to personalise AML treatments based on PAK inhibitors.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"135"},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626958","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":"Basal cell adhesion molecule (BCAM) promotes mesothelial-to-mesenchymal transition and tumor angiogenesis through paracrine signaling.","authors":"Suresh Sivakumar, Sonja Lieber, Raimund Dietze, Vanessa M Beutgen, Eileen C Sutor, Sophie Heidemann, Florian Finkernagel, Julia Teply-Szymanski, Andrea Nist, Thorsten Stiewe, Katrin Roth, Silke Reinartz, Johannes Graumann, Sabine Müller-Brüsselbach, Rolf Müller","doi":"10.1186/s12964-025-02128-9","DOIUrl":"10.1186/s12964-025-02128-9","url":null,"abstract":"<p><strong>Background: </strong>High expression of basal cell adhesion molecule (BCAM) is a hallmark of ovarian cancer (OC) progression. BCAM facilitates transcoelomic dissemination by promoting mesothelial cell clearance at peritoneal attachment sites of tumor cell spheroids. We investigated how BCAM mediates this effect and potentially drives other pro-metastatic functions.</p><p><strong>Methods: </strong>The impact of BCAM on the tumor cell secretome and the mesothelial cell phenotype was analyzed by affinity proteomics, bulk and single-cell RNA sequencing, life-cell and multiphoton microscopy, biochemical and functional in vitro assays as well as a murine tumor model. BCAM manipulation involved ectopic overexpression, inducible expression and treatment with soluble BCAM.</p><p><strong>Results: </strong>All forms of BCAM enhanced the secretion of cytokines that impact cell motility, mesenchymal differentiation and angiogenesis, including AREG, CXCL family members, FGF2, TGFB2, and VEGF. Notably, their levels in OC ascites were correlated with BCAM expression, and recombinant BCAM-induced cytokines triggered mesothelial-mesenchymal transition (MMT). Mesothelial cells undergoing MMT exhibited enhanced motility away from attaching tumor spheroids, leading to mesothelial clearance at spheroid attachment sites. BCAM-mediated MMT-associated transcriptional changes were also observed in subpopulations of omental mesothelial cells from OC patients, and were associated with poor survival. Consistent with the secretome data, BCAM induced endothelial tube formation in vitro and markedly promoted tumor angiogenesis in a mouse model.</p><p><strong>Conclusion: </strong>We have identified previously unknown functions of the BCAM-induced secretome potentially impacting distinct stages of OC metastasis. While BCAM's impact on MMT may facilitate initiation of micrometastases, neo-angiogenesis is essential for tumor growth. Taken together with the observed clinical adverse association, our findings underscore the potential of BCAM as a therapeutic target.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"136"},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626956","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":"Correction to: Endothelial-mesenchymal crosstalk drives osteogenic differentiation of human osteoblasts through Notch signaling.","authors":"Daria Perepletchikova, Polina Kuchur, Liubov Basovich, Irina Khvorova, Arseniy Lobov, Kseniia Azarkina, Nikolay Aksenov, Svetlana Bozhkova, Vitaliy Karelkin, Anna Malashicheva","doi":"10.1186/s12964-025-02118-x","DOIUrl":"10.1186/s12964-025-02118-x","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"133"},"PeriodicalIF":8.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617873","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":"Upregulated FSP1 by GPD1/1L mediated lipid droplet accumulation enhances ferroptosis resistance and peritoneal metastasis in gastric cancer.","authors":"Guoliang Lin, Qingnan Liu, Chengjie Xie, Ke Ding, Guanghua Mo, Lu Zeng, Fan Zhang, RuiXuan Liu, Lei Lu, Wei Hong, Yuling Mao, Haibo Su, Shuai Li","doi":"10.1186/s12964-025-02126-x","DOIUrl":"10.1186/s12964-025-02126-x","url":null,"abstract":"<p><p>To successfully metastasize, cancer cells must evade detachment induced cell death, known as anoikis. Unraveling the mechanisms that gastric cancer (GC) circumvent anoikis and achieve peritoneal metastasis especially during unanchored growth, could significantly improve patient outcomes. Our study reveals that GC cells exhibit increased lipid peroxidation, MDA production, and cell death during suspension culture, which can be mitigated by the intervention with liproxstatin-1 and ferrostatin-1. We discovered that oleic acid (OA) or adipocytes stimulate lipid accumulation in GC cells, thereby inhibiting lipid peroxidation and cell death. Lipid mass spectrometry confirmed an upregulation of triglyceride synthesis, indicating that the accumulation of lipid droplet may confer resistance to ferroptosis during suspension growth. In vitro assays demonstrated that OA not only induces lipid droplet accumulation but also upregulates the expression of ferroptosis suppressor protein 1 (FSP1), a process that can be abrogated by the double knockout of GPD1/1L genes. Additionally, we have demonstrated that a decrease in the ubiquitination of FSP1 in GC cells upon lipid droplet accumulation, as well as silencing or pharmacological targeting FSP1, promotes ferroptosis and disrupts the peritoneal metastatic potential of GC cells. Collectively, our findings highlight the potential of FSP1 as a promising therapeutic target for metastatic gastric cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"132"},"PeriodicalIF":8.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617875","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":"L- and D-Lactate: unveiling their hidden functions in disease and health.","authors":"Jianting Li, Peng Ma, Zhizhen Liu, Jun Xie","doi":"10.1186/s12964-025-02132-z","DOIUrl":"10.1186/s12964-025-02132-z","url":null,"abstract":"<p><p>Lactate, once considered a mere byproduct of anaerobic metabolism, is now recognized as a critical signaling molecule with diverse roles in physiology and pathology. There are two stereoisomers of lactate: L- and D-lactate. Recent studies have shown that disruptions in these two lactate stereoisomers have distinct effects on health and disease. L-lactate is central to glycolysis and energy transfer through the Cori cycle but also acts as the dominant lactylation isomer induced by glycolysis, influencing metabolism and cell survival. Although less studied, D-lactate is linked to metabolic disorders and plays a role in mitochondrial dysfunction and oxidative stress. This review focuses on both L- and D-lactate and examines their biosynthesis, transport, and expanding roles in physiological and pathological processes, particularly their functions in cancer, immune regulation, inflammation, neurodegeneration and other diseases. Finally, we assess the therapeutic prospects of targeting lactate metabolism, highlighting emerging strategies for intervention in clinical settings. Our review synthesizes the current understanding of L- and D-lactate, offering insights into their potential as targets for therapeutic innovation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"134"},"PeriodicalIF":8.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617874","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":"Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.","authors":"Rachael Pulica, Ahmed Aquib, Christopher Varsanyi, Varsha Gadiyar, Ziren Wang, Trevor Frederick, David C Calianese, Bhumik Patel, Kenneth Vergel de Dios, Victor Poalasin, Mariana S De Lorenzo, Sergei V Kotenko, Yi Wu, Aizen Yang, Alok Choudhary, Ganapathy Sriram, Raymond B Birge","doi":"10.1186/s12964-025-02090-6","DOIUrl":"10.1186/s12964-025-02090-6","url":null,"abstract":"<p><p>The negatively charged aminophospholipid, phosphatidylserine (PS), is typically restricted to the inner leaflet of the plasma membrane under normal, healthy physiological conditions. PS is irreversibly externalized during apoptosis, where it serves as a signal for elimination by efferocytosis. PS is also reversibly and transiently externalized during cell activation such as platelet and immune cell activation. These events associated with physiological PS externalization are tightly controlled by the regulated activation of flippases and scramblases. Indeed, improper regulation of PS externalization results in thrombotic diseases such as Scott Syndrome, a defect in coagulation and thrombin production, and in the case of efferocytosis, can result in autoimmunity such as systemic lupus erythematosus (SLE) when PS-mediated apoptosis and efferocytosis fails. The physiological regulation of PS is also perturbed in cancer and during viral infection, whereby PS becomes persistently exposed on the surface of such stressed and diseased cells, which can lead to chronic thrombosis and chronic immune evasion. In this review, we summarize evidence for the dysregulation of PS with a main focus on cancer biology and the pathogenic mechanisms for immune evasion and signaling by PS, as well as the discussion of new therapeutic strategies aimed to target externalized PS. We posit that chronic PS externalization is a universal and agnostic marker for diseased tissues, and in cancer, likely reflects a cell intrinsic form of immune escape. The continued development of new therapeutic strategies for targeting PS also provides rationale for their co-utility as adjuvants and with immune checkpoint therapeutics.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"131"},"PeriodicalIF":8.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607275","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":"Immunosenescence promotes cancer development: from mechanisms to treatment strategies.","authors":"Leihan Wang, Dong Tang","doi":"10.1186/s12964-025-02082-6","DOIUrl":"10.1186/s12964-025-02082-6","url":null,"abstract":"<p><p>The body's innate immune system plays a pivotal role in identifying and eliminating cancer cells. However, as the immune system ages, its functionality can deteriorate, becoming dysfunctional, inefficient, or even inactive-a condition referred to as immunosenescence. This decline significantly increases the risk of malignancies. While the pro-cancer effects of T-cell aging have been widely explored, there remains a notable gap in the literature regarding the impact of aging on innate immune cells, such as macrophages and neutrophils. This review seeks to address this gap, with emphasis on these cell types. Furthermore, although certain cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have demonstrated efficacy across a broad spectrum of cancers, elderly patients are less likely to derive clinical benefit from these treatments. In some cases, they may even experience immune-related adverse events (irAEs). While senolytic strategies have shown promise in exerting anti-cancer effects, their adverse reactions and potential off-target effects present significant challenges. This review aims to elucidate the pro-cancer effects of immunosenescence, its implications for the efficacy and safety of ICIs, and potential anti-aging treatment strategies. In addition, optimizing anti-aging therapies to minimize adverse reactions and enhance therapeutic outcomes remains a critical focus for future research endeavors.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"128"},"PeriodicalIF":8.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598492","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":"Neuroprotective role and mechanistic insights of DJ-1 dimerization in Parkinson's disease.","authors":"Lingling Lv, Hainan Zhang, Jieqiong Tan, Chunyu Wang","doi":"10.1186/s12964-025-02136-9","DOIUrl":"10.1186/s12964-025-02136-9","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily driven by the degeneration of dopaminergic neurons, with limited therapeutic interventions currently available. Among the critical factors in PD pathogenesis, DJ-1, a multifunctional protein, has emerged as a key neuroprotective agent against oxidative stress-a major contributor to the disease. Recent research has emphasized the pivotal role of DJ-1 dimerization in enhancing its neuroprotective capabilities. This review provides an in-depth analysis of the molecular mechanisms underlying DJ-1 dimerization and its relevance to PD. Specifically, we specifically explore how dimerization stabilizes DJ-1, enhances its antioxidative properties, improves mitochondrial function, and modulates key cellular pathways essential for neuronal survival. Furthermore, we discuss the molecular determinants governing DJ-1 dimerization, highlighting its potential both as a biomarker for PD diagnosis and a promising therapeutic target. By synthesizing current advancements, we propose that targeting DJ-1 dimerization may offer innovative strategies to slow PD progression and bolster neuronal health. This review positions DJ-1 as a central focus in PD research, paving the way for future studies aimed at developing neuroprotective therapies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"129"},"PeriodicalIF":8.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598502","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":"SLC25A35 enhances fatty acid oxidation and mitochondrial biogenesis to promote the carcinogenesis and progression of hepatocellular carcinoma by upregulating PGC-1α.","authors":"Heng-Chao Yu, Lu Bai, Liang Jin, Yu-Jia Zhang, Zi-Han Xi, De-Sheng Wang","doi":"10.1186/s12964-025-02109-y","DOIUrl":"10.1186/s12964-025-02109-y","url":null,"abstract":"<p><p>Mitochondria dysfunction has been closely linked to a wide spectrum of human cancers, whereas the molecular basis has yet to be fully understood. SLC25A35 belongs to the SLC25 family of mitochondrial carrier proteins. However, the role of SLC25A35 in mitochondrial metabolism reprogramming, development and progression in human cancers remains unclear. Here, we found that SLC25A35 markedly reprogramed mitochondrial metabolism, characterized by increased oxygen consumption rate and ATP production and decreased ROS level, via enhancing fatty acid oxidation (FAO). Meanwhile, SLC25A35 also enhanced mitochondrial biogenesis characterized by increased mitochondrial mass and DNA content. Mechanistic studies revealed that SLC25A35 facilitated FAO and mitochondrial biogenesis through upregulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) via increasing acetyl-CoA-mediated acetylation of PGC-1α. Clinically, SLC25A35 was highly expressed in HCC and correlated with adverse patients' survival. Functionally, SLC25A35 promoted the proliferation and metastasis of HCC cells both in vitro and in vivo, as well as the carcinogenesis in a DEN-induced HCC mice model. Moreover, we found that SLC25A35 upregulation is caused, at least in part, by decreased miR-663a in HCC cells. Together, our results suggest a crucial oncogenic role of SLC25A35 in HCC by reprogramming mitochondrial metabolism and suggest SLC25A35 as a potential therapeutic target for the treatment of HCC.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"130"},"PeriodicalIF":8.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598518","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}