Molecular and Cellular Biochemistry最新文献

{"title":"Cancer-associated fibroblasts drive immune resistance in MSS colorectal cancer via the FAIM2-CES1-ER stress pathway.","authors":"Ren Tang, Hongtao Wan, Menglan Zhong, Kangpeng Yan, Bin Xu, Jianyong Xiong","doi":"10.1007/s11010-026-05705-9","DOIUrl":"10.1007/s11010-026-05705-9","url":null,"abstract":"<p><p>Microsatellite-stable (MSS) colorectal cancer (CRC) shows limited responsiveness to immune checkpoint inhibitors, often in the context of a fibrotic and immunosuppressive tumor microenvironment. Cancer-associated fibroblasts (CAFs) are central to extracellular matrix (ECM) remodeling, yet the underlying regulatory mechanisms remain unclear. Here, we identify Fas apoptotic inhibitory molecule 2 (FAIM2) as a stromal regulator that is downregulated in MSS CRC and associated with immune infiltration and patient prognosis. Single-cell RNA sequencing localizes FAIM2 predominantly to CAFs, where it inversely correlates with collagen production. Functional studies in L-929 cells and primary CAFs show that FAIM2 overexpression suppresses endoplasmic reticulum (ER) stress signaling and reduces collagen I and matrix metalloproteinase 2 (MMP2) expression; these effects are attenuated by the ER stress inducer Tunicamycin. Conversely, FAIM2 knockdown enhances ER stress and collagen synthesis, which are mitigated by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Mechanistically, carboxylesterase 1 (CES1) is identified as a downstream effector negatively regulated by FAIM2, mediating ER stress and ECM remodeling. In vivo, FAIM2 overexpression restrains tumor growth, reduces collagen deposition, and promotes tertiary lymphoid structure (TLS) formation, whereas CES1 co-overexpression counteracts these effects. Together, these findings reveal a potential FAIM2-CES1-ER stress axis in CAFs associated with ECM remodeling and immune contexture in MSS CRC, providing a rationale for future studies exploring its therapeutic potential in immunotherapy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5437-5454"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977207","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":"METTL7B attenuates pathological cardiac hypertrophy via m6A-associated regulation of HK3.","authors":"Zhen Bao, Zhi-Qiang Liu, Yu-Chun Yang, Kai Wang, Muhuyati Wulasihan","doi":"10.1007/s11010-026-05737-1","DOIUrl":"10.1007/s11010-026-05737-1","url":null,"abstract":"<p><p>Pathological cardiac hypertrophy is a major contributor to heart failure, yet the epitranscriptomic mechanisms that restrain maladaptive remodeling remain incompletely understood. In this study, we investigated the role of METTL7B and its association with m6A-related regulation of HK3 in pathological cardiac hypertrophy. By integrating RNA-seq and MeRIP-seq data from human hypertrophic and failing hearts, we identified coordinated downregulation of METTL7B and HK3, accompanied by reduced m6A enrichment of HK3 transcripts. Additional analysis of an independent human hypertrophic cardiomyopathy dataset showed a positive correlation between METTL7B and HK3 expression. These findings were further validated in angiotensin II-treated AC16 cardiomyocytes. Functional studies showed that overexpression of either METTL7B or HK3 attenuated cardiomyocyte hypertrophy in vitro and alleviated transverse aortic constriction-induced cardiac remodeling and dysfunction in vivo. RNA pull-down assays showed enrichment of METTL7B in HK3 RNA pull-down complexes, and METTL7B overexpression was accompanied by increased HK3 m6A enrichment and restored HK3 expression under hypertrophic stress. In vitro rescue experiments showed that HK3 silencing partially counteracted the anti-hypertrophic effect of METTL7B overexpression, supporting HK3 as a functional downstream effector of METTL7B in cardiomyocytes. We also identified YTHDC1 as a candidate HK3 RNA-associated factor. YTHDC1 knockdown stabilized HK3 mRNA, increased HK3 abundance, and reduced hypertrophic marker expression in METTL7B-overexpressing cardiomyocytes. Collectively, these findings identify a METTL7B-HK3 regulatory relationship in pathological cardiac hypertrophy and implicate YTHDC1 as a potential modulator of HK3 regulation. Our study suggests that METTL7B suppresses hypertrophic remodeling, at least in part, in association with m6A-associated regulation of HK3.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5495-5514"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977302","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":"Opportunities in cancer gene therapy: inhibiting MDM2 and restoring p14ARF as a means to activate p53.","authors":"Soraia Barbosa de Oliveira, Ana Laura Vieira Alves, Bianca Naomi Niitsuma, Fernanda Antunes, Gabriel Borel Marinho, Giovanna Lagonegro Amanatidis, Jean Luz, Mariana Barbosa, Pedro Egydio Oliveira Zambotti, Otavio Augusto Rodrigues, Bryan E Strauss","doi":"10.1007/s11010-026-05742-4","DOIUrl":"10.1007/s11010-026-05742-4","url":null,"abstract":"<p><p>The MDM2/p53/p14ARF axis represents a central regulatory network controlling cell-cycle progression, genomic stability, and tumor suppression, and is frequently deregulated in human cancers. In many malignancies, particularly those retaining wild-type TP53, p53 activity is functionally suppressed through MDM2 overexpression or CDKN2A (p14ARF) loss, events that may be reversed in order to activate this pathway. This review explores the biological basis of the MDM2/p53/p14ARF axis and its relevance as a target for gene therapy and multimodal treatment strategies. While gene therapy for the restoration of p53 has been extensively explored, the use of genetic interventions for the inhibition of MDM2 or the restoration of p14ARF is underrepresented, though they have the potential to re-establish DNA damage responses, promote apoptosis, and enhance tumor sensitivity to chemotherapy and radiotherapy. In addition, p53 activation is now recognized as a contributor to immunogenic cell death and modulation of the tumor microenvironment. Laboratory and early clinical studies demonstrate that inhibition of MDM2 and restoration of p14ARF by gene transfer can integrate tumor cytotoxicity with immune activation. Although large-scale clinical validation remains limited, current evidence supports the MDM2/p53/p14ARF axis as a promising, context-dependent target within biomarker-driven combination therapies rather than a standalone approach.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5125-5143"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017642","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":"Curcumin improves myocardial redox status in an experimental model of rheumatoid arthritis.","authors":"Katarina Djordjevic, Bozidar Pindovic, Katarina Mihajlovic, Jelena Terzic, Djurdjina Petrovic, Andjela Milojevic-Samanovic, Zorka Stanic, Katarina Postolovic, Maja Barudzija, Ranko Skrbic, Milos Stojiljkovic, Vladimir Jakovljevic, Tamara Nikolic Turnic","doi":"10.1007/s11010-026-05717-5","DOIUrl":"10.1007/s11010-026-05717-5","url":null,"abstract":"<p><p>Curcumin, a natural polyphenol derived from turmeric, possesses potent antioxidant properties and represents a potential cardioprotective agent capable of mitigating myocardial oxidative stress associated with rheumatoid arthritis (RA). The aim of the study was to examine the cardioprotective effect of curcumin in an experimental model of rheumatoid arthritis. The study included 104 female Wistar albino rats, divided into 8 groups (n = 13 in each group): (1) CTRL (negative control, healthy rats without treatment), (2) CUR (positive control 1, curcumin 200 mg/kg three times a week for 4 weeks orally), (3) MTX (positive control 2, methotrexate 0.75 mg/kg twice a week for 4 weeks intraperitoneally), (4) RA (positive control 3, rats with Complete Freund's adjuvant (CFA)-induced RA), (5) RA+pCUR (rats with preventive administration of curcumin + CFA-induced RA), (6) RA+tCUR (rats with CFA-induced RA + therapeutic administration of curcumin), (7) RA + MTX+pCUR (rats with preventive administration of curcumin + CFA-induced RA + methotrexate), (8) RA + MTX+tCUR (rats with CFA-induced RA + therapeutic administration of curcumin + methotrexate). Pro-oxidant levels were determined in coronary venous effluent, antioxidant enzyme activities were assessed in heart tissue homogenates, and histopathological analyses of the synovium and myocardium were performed. Curcumin, particularly in the therapeutic regimen and in combination with methotrexate, significantly reduced pro-oxidant levels and lipid peroxidation. Curcumin also increased superoxide dismutase activity and restored reduced glutathione levels, whereas improvement in catalase activity was observed predominantly in the therapeutic regimens. Histopathological analyses demonstrated that curcumin exerted a protective effect on both synovial and myocardial tissues, attenuating RA-induced structural damage, reducing edema, and preserving myocardial architecture. These findings suggest that curcumin improves myocardial redox homeostasis and may contribute to cardioprotection in experimental RA.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5263-5285"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900821","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":"Mitochondria-mediated anticancer effects of two previously characterized COX-2 inhibitors in hepatocellular carcinoma.","authors":"Roya Mirzaei, Mahsa Manafi Varkiani, Mona Moosavi, Reza Habibi, Fereshteh Niknam, Mahsa Azami Movahed, Afshin Zarghi, Jalal Pourahmad","doi":"10.1007/s11010-026-05735-3","DOIUrl":"10.1007/s11010-026-05735-3","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and often shows limited response to current therapies like sorafenib. This study investigates the selective anticancer activity and mitochondria-mediated apoptotic effects of two previously characterized COX-2 inhibitors, ZMA-M3 (imidazo[1,2-a]pyrazine) and ZMA-M4 (imidazo[1,2-a]pyridine), in isolated HCC and normal rat hepatocytes. Isolated HCC and normal rat hepatocytes were treated with various concentrations of ZMA-M3 and ZMA-M4 to determine their half-maximal inhibitory concentrations (IC50). Apoptosis was evaluated using Annexin V-FITC/PI staining and caspase-3 activity assays. Mitochondrial dysfunction was assessed by measuring reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release. Isolated HCC and normal rat hepatocytes were treated with various concentrations of ZMA-M3 and ZMA-M4 to determine their half-maximal inhibitory concentrations (IC50). Apoptosis was evaluated using Annexin V-FITC/PI staining and caspase-3 activity assays. Mitochondrial dysfunction was assessed by measuring reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5419-5435"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945311","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":"18β-glycyrrhetinic acid ameliorates ifosfamide-induced nephrotoxicity by suppressing Wnt3a/IL-17A-driven inflammatory signaling, ER stress, and apoptosis while preserving ZO-1 integrity.","authors":"Fatih Mehmet Kandemir, Hasan Şimşek, Tuğba Çelik Samancı, Özge Kandemir","doi":"10.1007/s11010-026-05748-y","DOIUrl":"10.1007/s11010-026-05748-y","url":null,"abstract":"<p><p>Ifosfamide (IFO) is an effective chemotherapeutic agent, but its clinical use is limited by dose-dependent nephrotoxicity. This study investigated the protective effects of 18β-glycyrrhetinic acid (18β-GA) against IFO-induced acute renal injury and explored the underlying molecular mechanisms. Twenty-eight male Wistar albino rats were divided into four groups: Control, 18β-GA, IFO, and IFO+18β-GA. 18β-GA was administered orally at 100 mg/kg/day for two consecutive days, while nephrotoxicity was induced by a single intraperitoneal injection of IFO at 500 mg/kg. Renal function markers, oxidative stress parameters, inflammatory and apoptotic gene expression, Wnt3a/IL-17 A/ACT1/TRAF6 and Notch/HES1 signaling pathways, histopathological alterations, ZO-1 integrity, and CHOP expression were evaluated. IFO markedly impaired renal function, increased serum urea and creatinine levels, enhanced lipid peroxidation, depleted antioxidant defenses, and induced severe histopathological damage. IFO also upregulated NF-κB, TNF-α, Bax, Caspase-3, Wnt3a, IL-17 A, ACT1, TRAF6, Notch, and HES1 expression, while reducing Bcl-2 expression. In addition, IFO increased CHOP immunoreactivity and disrupted ZO-1 expression in tubular epithelial cells. Co-treatment with 18β-GA significantly improved renal function, restored antioxidant capacity, and was associated with the suppression of inflammatory and apoptotic signaling, downregulation of Wnt3a/IL-17 A/ACT1/TRAF6 and Notch/HES1 activation, reduced CHOP expression, preserved ZO-1 immunoreactivity, and ameliorated renal histological injury. These findings suggest that 18β-GA exerts potential multi-target renoprotective effects against IFO-induced nephrotoxicity by modulating oxidative stress, inflammation, ER stress, apoptosis, developmental signaling, and epithelial junctional integrity.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5591-5604"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017698","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":"Anti-inflammatory activity of Chlorella polysaccharide AHP.","authors":"Bingfeng Zhou, Su Liang, Jianmei Ou, Changhua Shang","doi":"10.1007/s11010-026-05726-4","DOIUrl":"10.1007/s11010-026-05726-4","url":null,"abstract":"<p><p>Current medications for inflammatory bowel disease (IBD) are associated with various side effects. Researches had shown that bioactive substances (such as polysaccharides) exhibited anti-inflammatory activity, immunomodulatory activity and the property of the regulation of gut microbiota, which could contribute to the repair of colonic tissue and the improvement of intestinal health. The bioactive substances provided a new direction for developing safe, effective and novel therapeutic strategies. Therefore, the objective of this study was to evaluate the efficacy and safety of Chlorella polysaccharide AHP for the treatment of Caco-2 cell injury and ulcerative colitis in mice. This study investigated the anti-inflammatory activity of polysaccharide extracted from Chlorella (AHP) and its mechanisms through in vitro and in vivo experiments. In vitro, AHP significantly reduced reactive oxygen species (ROS) level, suppressed apoptosis and downregulated the levels of proinflammatory factors in dextran sulfate sodium (DSS)-induced Caco-2 cells, demonstrating antioxidant and anti-inflammatory effects. In vivo, AHP alleviated pathological damage of colon, decreased oxidative stress and levels of pro-inflammatory cytokines, enhanced expression of tight junction proteins and repaired intestinal mucosal barrier in mice with DSS-induced colitis. Furthermore, AHP modulated gut microbiota composition and levels of related metabolites, contributing to its anti-inflammatory activity through microecological regulation. These findings indicated that AHP mitigated DSS-induced cell injury and colonic damage via multiple pathways, confirming its potent anti-inflammatory properties through in vitro and in vivo experiments. This study provided important theoretical basis for exploring new treatments of IBD with bioactive substance AHP and developing functional foods based on AHP.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5723-5743"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081529","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":"Ellagic acid attenuates myocardial fibrosis by suppressing Bmi1-mediated inhibition of the p53/p21 pathway in cardiac fibroblasts.","authors":"Bolin Li, Chongyu Shao, Xiaoxiao Huang, Huifen Zhou, Kai Huang, Chengsi Jin, HaiTong Wan","doi":"10.1007/s11010-026-05720-w","DOIUrl":"10.1007/s11010-026-05720-w","url":null,"abstract":"<p><p>Myocardial fibrosis is characterized by excessive cardiac fibroblasts (CF) proliferation and extracellular matrix deposition. The p53 tumor suppressor is known to inhibit CF proliferation, while the polycomb protein Bmi1 negatively regulates p53. Ellagic acid (EA), a natural polyphenol, has demonstrated anti-fibrotic potential, but its mechanism of action in the heart remains unclear. This study investigated whether EA reduces myocardial fibrosis by inhibiting Bmi1 expression. A rat model of myocardial fibrosis was established using isoproterenol (ISO), and rat cardiac fibroblasts were treated with TGF-β to induce a pro-fibrotic phenotype in vitro. Echocardiography and histology confirmed that EA treatment improved cardiac function and reduced fibrosis in ISO-induced rats. In vitro, EA significantly inhibited TGF-β-induced CF proliferation, migration, and differentiation into myofibroblasts. Mechanistically, EA upregulated p53 and its downstream target p21, leading to G1/S cell cycle arrest. Molecular docking and dynamics simulations predicted that EA binds to Bmi1, and subsequent experiments showed EA treatment reduced Bmi1 protein levels. Using a Bmi1 inhibitor (PTC-209) and overexpression plasmids, we demonstrated that the anti-fibrotic effects of EA are mediated in part through inhibition of Bmi1, which in turn activates the p53 pathway. Ellagic acid reduces myocardial fibrosis, at least in part, through suppression of Bmi1 expression. This suppression is associated with relief of the inhibitory effect of Bmi1 on p53, leading to p53/p21 pathway activation, cell cycle arrest, and subsequent inhibition of cardiac fibroblasts proliferation, migration, and differentiation. These findings suggest that Bmi1 may represent a novel therapeutic target for EA treatment of myocardial fibrosis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5301-5317"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900881","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":"Laminin-triggered integrin signaling potentiates γ-enolase-induced neurite outgrowth.","authors":"Selena Horvat, Urša Pečar Fonović, Janko Kos, Anja Pišlar","doi":"10.1007/s11010-026-05755-z","DOIUrl":"10.1007/s11010-026-05755-z","url":null,"abstract":"<p><p>Neurite growth is regulated by trophic support and the extracellular matrix (ECM). γ-Enolase, a neuron-specific enolase isoform, promotes neurite outgrowth through neurotrophic-like activity, but the contribution of ECM engagement and integrin signaling remains unclear. Here, we examined the role of laminin, collagen, and poly-L-lysine in γ-enolase peptide-induced neuritogenesis in neuroblastoma SH-SY5Y and pheochromocytoma PC12 cells. Treatment with a synthetic C-terminal γ-enolase peptide (γ-Eno) rapidly induced neurite outgrowth and actin remodeling, with laminin providing the strongest enhancement, particularly in SH-SY5Y cells. γ-Eno increased surface expression of β1 integrin and, to a lesser extent, α1 integrin, alongside a stronger neurite response on laminin. In laminin-coated cells, actin remodeling was evident within 3 h, followed by increased neurite formation at 24 h and significant neurite elongation at 48 h. Mechanistically, γ-Eno induced focal adhesion kinase (FAK) phosphorylation, which was significantly increased in both cell types on laminin and collagen. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was cell type- and ECM-dependent, whereas Akt phosphorylation increased significantly in SH-SY5Y cells but did not change markedly in PC12 cells. Integrin blockade with GRGDS attenuated γ-Eno-induced neurite outgrowth, MAP2 expression, and FAK phosphorylation. GRGDS also reduced Akt phosphorylation in SH-SY5Y cells and attenuated ERK1/2 phosphorylation in PC12 cells, supporting cell type-specific downstream signaling. These findings show that laminin-mediated integrin signaling enhances γ-enolase-induced neurite outgrowth and is associated with integrin-dependent FAK activation, with ERK1/2 and Akt contributing in a context-dependent manner.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5745-5760"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112191","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":"NRF2 signaling drives chemoresistance in NSCLC and glioblastoma.","authors":"Izadora de Souza, Linda Karolynne Seregni Monteiro, Ana Beatriz da Silva Teixeira, Camila Banca Guedes, Karoline Almeida Lima, Cláudio Henrique Dahne de Souza Filho, Izabela Amélia Marques de Andrade, Maria Carolina Clares Ramalho, Beatriz Silva de Oliveira, Mariana Lazarini, Clarissa Ribeiro Reily Rocha","doi":"10.1007/s11010-026-05747-z","DOIUrl":"10.1007/s11010-026-05747-z","url":null,"abstract":"<p><p>Although great advances have been made in cancer treatment, lung cancer and glioblastoma patients continue to present a dismal prognosis, mainly due to drug resistance. Evidence suggests that NRF2 and glutathione (GSH) play a fundamental role in chemotherapy resistance. Notably, GSH depletion by buthionine sulfoximine (BSO) has been demonstrated to sensitize human tumor cells to a wide variety of chemotherapeutic agents. However, the incorporation of BSO into standard chemotherapy regimens lacks a robust clinical rationale. In this study, we aimed to investigate the mechanisms governing differential sensitivity to chemotherapy in lung cancer and glioblastoma cells to identify novel strategies to enhance outcomes in these malignancies. For this purpose, we analyzed several cellular responses in cell lines exhibiting distinct sensitivities to temozolomide (TMZ) and cisplatin. Our findings indicate that the NRF2/GSH pathway plays a crucial role in TMZ and cisplatin resistance and that pharmacological GSH depletion enhances the sensitivity of NRF2-high, chemotherapy-resistant cells to these agents. Furthermore, BSO in combination with TMZ or cisplatin enhanced chemotherapy-induced cytotoxicity and engaged both apoptotic and ferroptosis-related responses in NSCLC cells. These findings provide preclinical evidence supporting further investigation of NRF2/GSH targeting as a strategy to overcome chemotherapy resistance.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5577-5590"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008583","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}