Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Heat shock protein 70 regulates m6A modification in response to heat shock in esophageal squamous cell carcinoma.","authors":"Bin Du, Jia Wang, Jun Ma, Pu Wang","doi":"10.1016/j.bbamcr.2025.120027","DOIUrl":"10.1016/j.bbamcr.2025.120027","url":null,"abstract":"<p><p>Heat shock has been known to induce hyperplasia in esophageal epithelial cells. It is widely considered as a crucial risk factor in the initiation and development of esophageal squamous cell carcinoma (ESCC), yet our understanding of the underlying mechanisms remains limited. The m6A modification of mRNA plays a role in mediating several cellular processes and is critical during cell stress. Our study revealed that inhibiting of m6A 'writer' components of ESCC cells exhibit higher death rates and slower recovery after heat shock. After normalization using mRNA expression profiles, 91.08 % of significantly changed m6A modifications aligned with corresponding mRNA abundance changes, with no evidence of over-modification, while the increase in m6A modification of 8.92 % of heat-shock associated genes far exceeded the increase in mRNA (hyper - m6A modification), and A/U rich motifs were commonly observed in the 3'UTR of these gene. Inside the nucleus, the binding of HSP70s in m6A writer complex promote the hyper - m6A modification in specific mRNAs after heat shock. The stronger nuclear localization of HSP70 in ESCC tissues correlates with a poor prognosis for the patients. In conclusion, our research revealed that the nuclear HSP70 protein could bind to the METTL3/14 writer complex and regulate mRNA's m6A modification. Our results provide a new perspective for research into how HSP70 protein regulates mRNA stability and suggests a new direction for the comprehensive prevention and treatment of ESCC.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"120027"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts secreting IL-6 inhibit the cisplatin and docetaxel killing effect in lung squamous cell carcinoma.","authors":"Xu Zhu, Long Li, Xuanyin Wang, Ying Zhang, Zeyang Yang, Jiaming Ren, Lu Wang, Xianling Zeng, Jing Xiao, Siyu Wang, Peiying Pan, Jian Zhang, Xiaojun Du, Tao Wang, Langbo Liu, Xiaolin Shu, Qiaoling Zhang, Jiangwei Wu, Siyuan Yang, Xinlei Liu, Zhu Zeng, Jieheng Wu","doi":"10.1016/j.bbamcr.2025.120029","DOIUrl":"10.1016/j.bbamcr.2025.120029","url":null,"abstract":"<p><p>Chemoresistance remains a major obstacle in the treatment of lung squamous cell carcinoma (LUSC), often leading to suboptimal clinical outcomes. Among the key contributors to this resistance are cancer-associated fibroblasts (CAFs), which are increasingly recognized for their tumor-supportive roles. Despite this, the molecular pathways through which CAFs promote chemoresistance in LUSC are not fully elucidated. This study found that CAFs-derived interleukin-6 (IL-6) upregulated the expression of Specificity Protein 1 (SP1) and the ATP-binding cassette transporter B7 (ABCB7) in LUSC cells exposed to cisplatin and docetaxel. In vitro assays showed a marked decrease in apoptosis in tumor cells co-cultured with CAFs. Consistent with these findings, in vivo xenograft models demonstrated that IL-6-producing CAFs reduced the antitumor efficacy of both chemotherapeutic agents. Elevated serum IL-6 levels also emerged as a potential indicator of poor response to chemotherapy. Our findings suggest that IL-6 secreted by CAFs impairs the cytotoxic effects of cisplatin and docetaxel in LUSC, partly through activation of the PI3K/AKT/NF-κB signaling axis. Targeting this IL-6-mediated pathway may offer a promising strategy to overcome chemoresistance and enhance therapeutic outcomes in patients with LUSC.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"120029"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arabidopsis thaliana loss-of-function chloroplast tata mutants display an albino phenotype indicating a chloroplast-only function","authors":"Sarah Jessup ,&nbsp;Ruchira Sepali Mallawa Arachchi ,&nbsp;Chris Carrie","doi":"10.1016/j.bbamcr.2025.120068","DOIUrl":"10.1016/j.bbamcr.2025.120068","url":null,"abstract":"<div><div>A functional mitochondrial Tat (mtTat) pathway has been confirmed in plants, but the existence or need for a TatA subunit remains unanswered.</div><div>Two competing hypotheses have suggested that either plant mitochondria contain an unusual Tat pathway with no TatA contribution, or the chloroplast TatA (cpTatA) is dually targeted to chloroplasts and mitochondria.</div><div><em>Arabidopsis thaliana cptata</em> loss-of-function mutants display an albino phenotype consistent with a dysfunctional chloroplast Tat pathway with no quantitative impact on mitochondrial complex III biogenesis, reiterating a chloroplast-specific role of cpTatA.</div><div>While these findings reject the dual-targeting hypothesis, the roles and components of the plant mitochondrial Tat pathway are yet to be fully elucidated.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120068"},"PeriodicalIF":3.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of androgen receptor splice variant target gene expression in prostate cancer","authors":"Neele Wüstmann,&nbsp;Julissa Reimann,&nbsp;Julia Vieler,&nbsp;Verena Humberg,&nbsp;Katrin Schlack,&nbsp;Martin Bögemann,&nbsp;Andres Jan Schrader,&nbsp;Christof Bernemann","doi":"10.1016/j.bbamcr.2025.120062","DOIUrl":"10.1016/j.bbamcr.2025.120062","url":null,"abstract":"<div><div>This study aimed to comprehensively analyze AR-V specific target gene expression using a physiological system that simulates the actual situation of AR-FL and AR-V co-appearance in prostate cancer patients. Clinically described AR splice variants AR-V3, AR-V7 and AR-V9 were transfected along with AR-FL in AR-negative prostate cancer PC-3 cells. RNA sequencing analysis showed only slight differences in differentially expressed genes between AR-FL and AR-V co-expressing cells compared to solely AR-FL expressing cells. Immunofluorescence analysis and luciferase assays revealed hormonal dependency of AR-FL, constitutive activity of AR-V7, and ambivalent activity of AR-V9, while AR-V3 showed no activity. Analysis of a set of published target genes showed steady upregulation of EDN2 and FKBP5. Yet, clinical analysis revealed no significant differences in overall survival data in prostate cancer patients. The study challenges the existence of an AR-V specific transcriptome responsible for treatment resistance and tumor progression and highlights the need for further investigation into the molecular mechanism by which AR-V proteins route resistance to ARTA treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120062"},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma membrane Bile acid TGR5 receptor specific stimulation induces Ca²⁺ mobilisation, ATP secretion and P2Y receptors activation in cholangiocytes.","authors":"Xuanmeng Chen, Amr Al-Shebel, Thibault Pebrier, Thierry Tordjmann, Olivier Dellis","doi":"10.1016/j.bbamcr.2025.120067","DOIUrl":"https://doi.org/10.1016/j.bbamcr.2025.120067","url":null,"abstract":"<p><p>The Bile Acid receptor TGR5 is well known to activate the cAMP pathway leading to CFTR activation and Cl^- ions secretion, needed for bile alkalinization and hydration. However, during cystic fibrosis development, only 10 to 15 % of the patients present liver defects due to bile duct disorders, meaning that another process should compensate for the loss of CFTR activity. Interestingly, some bile acids had also been reported to mobilize Ca²⁺ ions in cholangiocytes. Using normal human cholangiocytes and cholangiocarcinoma cell lines, we confirmed by using a specific agonist, that TGR5 stimulation induced a Ca²⁺ release from the endoplasmic reticulum and an influx of extracellular Ca²⁺ ions. Next, this Ca²⁺ mobilisation allows an ATP (and UTP) release, leading to the activation of P2Y receptors, reinforcing this Ca²⁺ mobilisation. This study shows that activation of the BA receptor TGR5 has the capacity to induce the two main intracellular pathways, cAMP and IP₃-Ca²⁺ in cholangiocytes. From our data, we speculate that the pathway we described will allow activation of the Ca²⁺-activated Cl^- channels TMEM16A, to compensate in part or in totality the loss of CFTR in CF patients.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"120067"},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV4 is involved in progesterone-mediated sexual dimorphism in mesenchymal stem cell functions and bio-mineralization","authors":"Nishant Kumar Dubey ,&nbsp;Satish Kumar ,&nbsp;Shamit Kumar ,&nbsp;Subham Mishra ,&nbsp;Nilesh Kumar Das ,&nbsp;Chandan Goswami","doi":"10.1016/j.bbamcr.2025.120066","DOIUrl":"10.1016/j.bbamcr.2025.120066","url":null,"abstract":"<div><div>The prevalence of bone disorders in female has been linked with imbalances in sex hormones, especially during pregnancy and menopause. Apart from regulation of transcription, recent reports suggest the involvement of various ion channels which can also be the molecular targets of an array of steroids (and steroid-like molecules). The differences in steroid responses between males and females also impose the need to understand the complexity of steroid actions. This current <em>in vitro</em> study has been carried out during the osteoblast differentiation (day 1 and day 12, early and late time points respectively) using MSCs-derived from male and female animals and in the presence of progesterone (P4) and/or TRPV4 modulators to explore the existence of sexual dimorphism at the cellular level if any and possible involvement of TRPV4 and P4 in it. Different subcellular parameters such as cytosolic Ca²⁺, mitochondrial potential, cytosolic- and mitochondrial-ROS and functional assays such as bio-mineralization (BM) were performed. All these results point out that P4 modulates TRPV4 both in the short-term and long-term, but differently in male and female-derived primary cells. It is observed that P4 can modulate TRPV4 in a long-term, both transcription-dependent and transcription-independent manner. Thus, the observed sexual dimorphism at the cultured cellular system is more prominent in the early time point which seems to be dampened, but still exists in the later time points. These findings may be relevant for bone disorders due to hormonal imbalance.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120066"},"PeriodicalIF":3.7,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COA6 deficiency inhibits hepatocellular carcinoma progression by regulating cuproptosis through the JAK/STAT signaling pathway","authors":"Kailiang Tian ,&nbsp;Yang Yang ,&nbsp;Xiaohang Niu ,&nbsp;Xiaoming Wei ,&nbsp;Mingjin Zhang ,&nbsp;Yangliu Zhou ,&nbsp;Mingya Yang ,&nbsp;Haonan Sun ,&nbsp;Lixin Zhu ,&nbsp;Fubao Liu","doi":"10.1016/j.bbamcr.2025.120065","DOIUrl":"10.1016/j.bbamcr.2025.120065","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors with limited therapeutic strategies. COA6 is a mitochondria-associated protein that plays an important role in regulating tumor cuproptosis, but its role in HCC is currently unknown. In this study, we aimed to investigate the expression and potential mechanism of action of COA6 in HCC.</div></div><div><h3>Methods</h3><div>TCGA-LIHC database was analyzed for differentially expressed cuproptosis-related genes (CRGs) in HCC and prognostic value, which was validated by immunohistochemistry and Western blot. CCK8, flow cytometry, wound healing, transwell and subcutaneous graft tumor assays were performed to explore the function of COA6 in HCC. Impact of COA6 on cuproptosis was assessed by assay kit and Western blot. RNA-sequencing were used to determine molecular mechanism. Immunoprecipitation (Co-IP) and immunofluorescence were used to assess the relationship between COA6 and NDUFA4L2. western blotting was used to detect the effect of COA6 on the JAK-STAT pathway.</div></div><div><h3>Results</h3><div>COA6 was significantly overexpressed in HCC tissues and HCC cell lines and was closely associated with poor prognosis. Silencing COA6 significantly inhibited the malignant phenotype of HUH7 and HepG2 cells in vitro and tumor growth in vivo. Moreover, silencing COA6 promoted ROS accumulation and activated cuproptosis in HCC cells. Interestingly, we found that COA6 interacted with NDUFA4L2 and COA6 deficiency significantly inhibited the JAK-STAT signaling pathway.</div></div><div><h3>Conclusions</h3><div>In conclusion, our data show that COA6 was highly expressed in HCC, and silencing COA6 blocked the JAK-STAT signaling pathway and activated cuproptosis, and inhibits the malignant phenotype and tumor growth of HCC cells. Therefore, targeting COA6 may be a potential therapeutic approach to inhibit HCC progression.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120065"},"PeriodicalIF":3.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glaucoma-associated polymorphism M98K-OPTN sensitizes retinal cells to protein homeostasis stress through p62-mediated caspase activation","authors":"Swetha Medchalmi,&nbsp;Zuberwasim Sayyad ,&nbsp;Ghanshyam Swarup","doi":"10.1016/j.bbamcr.2025.120064","DOIUrl":"10.1016/j.bbamcr.2025.120064","url":null,"abstract":"<div><div>M98K polymorphism of OPTN is significantly associated with glaucoma in certain populations. This raises the possibility that M98K-OPTN alone is not sufficient to cause glaucoma, and it may require cooperation with other genetic or environmental factors to induce glaucoma. Loss of vision in glaucoma occurs due to the degeneration of retinal ganglion cells. Here, we have tested the hypothesis that M98K-OPTN may enhance the sensitivity of retinal cells to protein homeostasis stress. For this purpose, we have used M98K-OPTN expressing and wild-type (WT)-OPTN expressing clones of retinal 661W cells. Upon induction of protein homeostasis stress by a proteasome inhibitor MG132 (1–2 μM), M98K-OPTN expressing cells showed reduced survival, and enhanced caspase-8, caspase-9, and caspase-3 activation in comparison with WT-OPTN expressing cells. Compared to WT-OPTN expressing cells, M98K-OPTN expressing cells showed enhanced formation of p62/SQSTM1-positive aggregates and enhanced p62 protein level under conditions of protein homeostasis stress. Knockdown of p62 resulted in reduced caspase-9, caspase-8, and caspase-3 activation in M98K-OPTN expressing cells treated with proteasome inhibitor. Our results suggest that M98K-OPTN modulates protein homeostasis stress-induced signalling that mediates p62-dependent caspase activation, which leads to enhanced sensitivity of M98K-OPTN expressing retinal cells to protein homeostasis stress.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120064"},"PeriodicalIF":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-derived FN1 promotes peritoneal cavity metastasis of gastric cancer by inhibiting the Hippo signaling pathway via SDC4","authors":"Meixia Zhang,&nbsp;Mingyan He,&nbsp;Fan Du,&nbsp;Yingping Xie,&nbsp;Ye Liao,&nbsp;Xiaolin Pan","doi":"10.1016/j.bbamcr.2025.120063","DOIUrl":"10.1016/j.bbamcr.2025.120063","url":null,"abstract":"<div><div>Gastric cancer (GC) is a prevalent malignant tumor worldwide. Peritoneal cavity metastasis is recognized as a critical clinical feature of late-stage GC. Fibronectin 1 (FN1) is closely associated with the development and progression of various cancers. This study aimed to investigate the functions of FN1 and the underlying mechanisms in peritoneal cavity metastasis of GC. A bioinformatics reanalysis of the single-cell sequencing dataset GSE140182 was performed to explore the cellular signature in malignant ascites. Cell communication analysis was performed to identify the cell communication between macrophages and tumor cells. GC cells were cultured with supernatant from FN1-overexpressing macrophages to investigate the effects and potential mechanism of FN1 action on GC cells by Western blot (WB) assay, MTT assay, migration and invasion assay, clone formation assay, cell adhesion assay, and functional rescue experiments. To further validate the impact of FN1 on GC and its peritoneal cavity metastasis were carried out in vivo experiments. Cellular communication between macrophages and GC cells was mediated by FN1-SDC4. Overexpression of macrophage-derived FN1 facilitated the malignant phenotypes of GC cells and the peritoneal cavity metastasis of GC in vivo. Mechanistically, macrophage-derived FN1 inhibited the Hippo signaling pathway by enhancing the expression of SDC4 in GC cells. Knockdown of SDC4 reversed the tumor-promoting effects induced by macrophage-derived FN1. Our study revealed that macrophage-derived FN1 inhibited the Hippo signaling pathway by upregulating the expression of SDC4 in GC cells, thereby promoting peritoneal cavity metastasis of GC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120063"},"PeriodicalIF":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Inhibition of autophagy sensitises cells to hydrogen peroxide-induced apoptosis: Protective effect of mild thermotolerance acquired at 40 °C\" [Biochim. Biophys. Acta Mol. Cell Res. (2016) volume 1863(12) 3050-3064 / PMID: 27666506].","authors":"M Redza-Dutordoir, S Kassis, H Ve, M Grondin, D A Averill-Bates","doi":"10.1016/j.bbamcr.2025.120061","DOIUrl":"https://doi.org/10.1016/j.bbamcr.2025.120061","url":null,"abstract":"","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"120061"},"PeriodicalIF":3.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}