Molecular Carcinogenesis最新文献_第2页

SOAT1 Activates NLRP3 Inflammasome to Promote Cancer-Related Lymphangiogenesis and Metastasis via IL-1β/IL-1R-1 Axis in Oral Squamous Cell Carcinoma. SOAT1激活NLRP3炎性体，通过IL-1β/IL-1R-1轴促进口腔鳞状细胞癌相关淋巴管生成和转移

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23907

Chengzhi Zhao, Yuhao Wang, Zhishen Jiang, Shengzhao Guo, Liru Hu, Jian Pan, Fan Dan

{"title":"SOAT1 Activates NLRP3 Inflammasome to Promote Cancer-Related Lymphangiogenesis and Metastasis via IL-1β/IL-1R-1 Axis in Oral Squamous Cell Carcinoma.","authors":"Chengzhi Zhao, Yuhao Wang, Zhishen Jiang, Shengzhao Guo, Liru Hu, Jian Pan, Fan Dan","doi":"10.1002/mc.23907","DOIUrl":"10.1002/mc.23907","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer in the head and neck region, significantly impacting patient survival rates and quality of life. Lymph node (LN) metastasis is a lead contributor to the poor prognosis associated with OSCC. SOAT1 plays a critical role in cholesterol metabolism and has been implicated in various cancers, although its specific mechanisms in OSCC are poorly understood. Additionally, NLRP3 inflammasome has been identified as a factor that promotes cancer progression by influencing various processes involved in tumor development, with its activation linked to cancer metastasis. Lymphangiogenesis enhancing cancer metastasis has been identified in OSCC, while the molecule networks of regulating it remains unclear. In our study, we found that SOAT1 is overexpressed in OSCC and promotes proliferation, migration, and invasion of OSCC cells. Knockdown SOAT1 expression impaired OSCC progression both in vitro and in vivo, and reduced the rate of LN metastasis. RNA sequencing analysis revealed that NLRP3 is a downstream regulated by SOAT1, with NLRP3 inflammasome reactivation having recovered cancer malignancy inhibited by SOAT1 knockdown. Furthermore, we revealed that IL-1β, released by NLRP3 inflammasome activation, could directly bind to IL-1R-1 in lymphatic endothelial cells (LECs), and enhance tube formation capacity of LECs, indicating the potential role of NLRP3 inflammasome in promoting lymphangiogenesis and metastasis in OSCC. In conclusion, SOAT1 could promote OSCC malignancy and regulate the activation of NLRP3 inflammasome to increase the rate of lymphangiogenesis and cancer metastasis via IL-1β/IL-1R-1 axis in OSCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1039-1056"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hsa_circ_0000231 Accelerates Cell Autophagy and Promotes Cell Proliferation and Invasion of Colorectal Cancer via miR-140-3p/Bcl-2 Axis. Hsa_circ_0000231通过miR-140-3p/Bcl-2轴加速细胞自噬，促进结直肠癌细胞增殖和侵袭。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23906

Long Zhao, Haoran Zhang, Shuo Wang, Yushi Zhou, Kewei Jiang, Shan Wang, Yingjiang Ye, Bo Wang, Zhanlong Shen

{"title":"Hsa_circ_0000231 Accelerates Cell Autophagy and Promotes Cell Proliferation and Invasion of Colorectal Cancer via miR-140-3p/Bcl-2 Axis.","authors":"Long Zhao, Haoran Zhang, Shuo Wang, Yushi Zhou, Kewei Jiang, Shan Wang, Yingjiang Ye, Bo Wang, Zhanlong Shen","doi":"10.1002/mc.23906","DOIUrl":"10.1002/mc.23906","url":null,"abstract":"Accumulating evidence indicated that circular RNAs (circRNAs) directly sponge to microRNAs (miRNAs),(miRNAs), which in turn regulate the gene expression and affect the malignancy behavior at the posttranscriptional level. However, the expression levels, function, and mechanism of circ_0000231 in colorectal cancer (CRC) are largely unknown. The expression levels of circ_0000231, miR-140-3p, and Bcl-2 in 110 CRC tissues and matched normal colorectal tissues were detected by qRT-PCR method. circ_0000231 and Bcl-2 were suppressed by siRNA, and miR-140-3p was overexpressed by RNA mimics in CRC cell lines. The function-based experiments were conducted to detect the proliferation and migratory abilities in CRC cell lines. RNA pull-down, RNA immunoprecipitation (RIP), and dual-fluorescence reporter assay were conducted to verify the association among circ_0000231, miR-140-3p, and Bcl-2. Western blot analysis and mRFP-GFP-LC3 adenovirus were used to detect the autophagy level affected by circ_0000231, miR-140-3p, and Bcl-2 axis. Downregulated circ_0000231 significantly suppressed the proliferation and migratory abilities of CRC cells by suppressing autophagy and promoting G0/G1 phase arrest. Furthermore, RNA pull-down, RIP, and dual-fluorescence reporter assays confirmed that circ_0000231 regulates the expression of Bcl-2 by directly targeting miR-140-3p. More importantly, circ_0000231 promoted the levels of autophagy via the miR-140-3p/Bcl-2 axis in CRC. Our study demonstrated that circ_0000231, as a tumor promotor, enhances the level of autophagy by regulating Bcl-2 via targeting miR-140-3p. Moreover, circ_0000231 might serve as a diagnostic and prognostic indicator and a novel molecular target for CRC therapy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1025-1038"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPR87 Promotes Angiogenesis in Esophageal Squamous Cell Carcinoma via VEGFA Regulation. GPR87通过VEGFA调控促进食管鳞状细胞癌血管生成。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23909

Dengyan Zhu, Donglei Liu, Kai Wu, Xingdong Cheng, Yang Yang

{"title":"GPR87 Promotes Angiogenesis in Esophageal Squamous Cell Carcinoma via VEGFA Regulation.","authors":"Dengyan Zhu, Donglei Liu, Kai Wu, Xingdong Cheng, Yang Yang","doi":"10.1002/mc.23909","DOIUrl":"10.1002/mc.23909","url":null,"abstract":"The role and underlying mechanisms of G protein-coupled receptor 87 (GPR87) in esophageal squamous cell carcinoma (ESCC) remain unclear, despite its established oncogenic functions in other malignancies. This study examined the expression of GPR87 and its association with survival rate in ESCC using online databases. The expression of GPR87 in ESCC tissues was identified using immunohistochemistry, and a correlation analysis was carried out using ki-67 data. ESCC cells were transfected with GPR87 knockdown or overexpression plasmids, followed by functional assays such as, CCK-8 for cell viability, colony formation for proliferation, wound healing for migration, Transwell for invasion, and tube formation for angiogenesis. Western blot analysis was used to assess STAT3 phosphorylation and VEGFA expression. Additionally, a xenograft tumor model was established to investigate the effect of GPR87 on tumor growth in vivo. The findings demonstrated that GPR87 was highly expressed in ESCC tissues and its overexpression was associated with a poor patient survival. Transfection with a GPR87 overexpression plasmid increases the cell viability, invasion, proliferation, and angiogenesis of ESCC cells, while transfection with sh-GPR87 reversed these effects. Additionally, GPR87 controlled VEGFA expression levels by promoting STAT3 phosphorylation. Rescue trials further verified that GPR87 promotes the growth of ESCC by modulating STAT3. Moreover, in vivo studies validated that GPR87 knockdown suppressed tumor growth. In conclusion, the findings highlight GPR87 as a key regulator of VEGFA expression via STAT3 activation, contributing to ESCC malignancy. Targeting GPR87 may provide a potential therapeutic strategy for ESCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1057-1065"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of HTRA1 Promotes EMT and Anoikis Resistance in Colorectal Cancer via Activation of Hippo/YAP1 Pathway by Facilitating LATS2 Degradation. HTRA1的下调通过促进LATS2降解激活Hippo/YAP1通路促进结直肠癌的EMT和Anoikis耐药。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-26 DOI: 10.1002/mc.23933

Zhihang Jiang, Xiaoqing Li, Fuqiang Liu, Junfeng Li, Kun Yang, Shuman Xu, Zheng Jiang

{"title":"Downregulation of HTRA1 Promotes EMT and Anoikis Resistance in Colorectal Cancer via Activation of Hippo/YAP1 Pathway by Facilitating LATS2 Degradation.","authors":"Zhihang Jiang, Xiaoqing Li, Fuqiang Liu, Junfeng Li, Kun Yang, Shuman Xu, Zheng Jiang","doi":"10.1002/mc.23933","DOIUrl":"https://doi.org/10.1002/mc.23933","url":null,"abstract":"Epithelial-mesenchymal transition (EMT) and anoikis resistance are crucial characteristics for tumor cell metastasis. High-temperature requirement A1 (HTRA1) has been identified as a serine protease with chaperone functions, but its role in the regulation of EMT, anoikis resistance, and metastasis in colorectal cancer (CRC) remains poorly understood. In this study, we identified that HTRA1 was downregulated in CRC tissues, and its low expression was significantly associated with advanced TNM stage and poor prognosis. Loss of HTRA1 facilitated EMT and anoikis resistance in CRC cells, thereby potentiating metastatic potential both in vitro and in vivo. Conversely, HTRA1 overexpression produced opposite effects. Furthermore, we carried out RNA-seq and found that HTRA1 was probably involved in the regulation of Hippo/YAP1 pathway. HTRA1 overexpression led to increased phosphorylation of YAP1 and decreased nuclear translocation, which could be largely reversed by XMU-MP-1, an inhibitor of the Hippo pathway. Mechanistically, HTRA1 directly bound to and stabilized large tumor suppressor gene 2 (LATS2), a key kinase of the Hippo pathway, which contributed to the inactivation of YAP1. Restoring LATS2 expression in HTRA1-deficient CRC cells decreased EMT and anoikis resistance. Altogether, our findings unveiled the negative regulatory function of HTRA1 in CRC progression through the regulation of the Hippo/YAP1 pathway, and supported HTRA1 as a potential therapeutic target in CRC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EXPRESSION OF CONCERN: Growth Inhibition of Pancreatic Cancer Cells by Histone Deacetylase Inhibitor Belinostat Through Suppression of Multiple Pathways Including Hif, Nfkb, and Mtor Signaling In Vitro and In Vivo. 关注表达：组蛋白去乙酰化酶抑制剂Belinostat通过抑制包括Hif， Nfkb和Mtor信号在内的多种途径抑制胰腺癌细胞的生长，在体外和体内。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-25 DOI: 10.1002/mc.23927

引用次数: 0

A Transcriptional Variant of Anaplastic Lymphoma Kinase Promotes Apoptosis in Ovarian High-Grade Serous Carcinoma. 间变性淋巴瘤激酶的转录变异促进卵巢高级别浆液性癌的细胞凋亡。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-19 DOI: 10.1002/mc.23928

Ako Yokoi, Daigo Yoshimori, Yasuko Oguri, Miki Hashimura, Makoto Saegusa

{"title":"A Transcriptional Variant of Anaplastic Lymphoma Kinase Promotes Apoptosis in Ovarian High-Grade Serous Carcinoma.","authors":"Ako Yokoi, Daigo Yoshimori, Yasuko Oguri, Miki Hashimura, Makoto Saegusa","doi":"10.1002/mc.23928","DOIUrl":"https://doi.org/10.1002/mc.23928","url":null,"abstract":"The current study aims to delineate the role of a novel anaplastic lymphoma kinase (ALK) transcript, ALKATI, in ovarian high-grade serous carcinoma (HGSC). Overexpressed ALKATI exhibited both cytoplasmic and nuclear localization in HGSC cells, whereas full-length ALK was predominantly cytoplasmic. ALKATI interacts with the DNA repair protein, poly (ADP ribose) polymer 1 (PARP1), and cells stably overexpressing ALKATI (OE- ALKATI) were more sensitive to cisplatin-induced apoptosis. Consistent with this, cleaved PARP1 levels were higher in HGSC tissue samples in areas with nuclear ALK immunoreactivity. The ratio of antiapoptotic BCL2 relative to proapoptotic BAX was significantly increased in OE-ALKATI cells, despite the increase in apoptosis, suggesting that ALKATI-mediated apoptosis is independent of mitochondrion-driven cell death. OE-ALKATI decreased epithelial-mesenchymal transition/cancer stem cell properties but did not alter proliferation rates, and nuclear ALK immunopositivity was not associated with clinicopathological factors or prognosis in HGSC. Together, our observations suggest that ALKATI sensitizes HGSC cells to apoptosis (probably though an association with PARP1) but this may have a relatively minor impact on tumor progression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Causal Relationship Between Blood Metabolites and Prostate Cancer Risk: A Two-Sample Mendelian Randomization Study. 血液代谢物与前列腺癌风险的因果关系：一项双样本孟德尔随机研究。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-19 DOI: 10.1002/mc.23929

Shuai Liu, Jingjing Zhu, Huizhen Zhang, Hua Zhong, Hoi Tung Hilton Wong, Liang Wang, Lang Wu

{"title":"Causal Relationship Between Blood Metabolites and Prostate Cancer Risk: A Two-Sample Mendelian Randomization Study.","authors":"Shuai Liu, Jingjing Zhu, Huizhen Zhang, Hua Zhong, Hoi Tung Hilton Wong, Liang Wang, Lang Wu","doi":"10.1002/mc.23929","DOIUrl":"https://doi.org/10.1002/mc.23929","url":null,"abstract":"Recent research has increasingly suggested an association between changes in specific blood metabolites and prostate cancer (PCa) development. However, it remains unclear whether these observed associations represent a causal relationship. To reveal the potential causal associations between blood metabolites and PCa risk, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis. We used genetic instruments for 514 and 490 metabolites from two independent comprehensive genome-wide association studies. These studies included 14,295 individuals of European ancestry from the INTERVAL/EPIC-Norfolk cohorts and 8299 individuals of European ancestry from the Canadian Longitudinal Study on Aging cohort. Summary statistics of PCa risk involving 122,188 cases and 604,640 controls of European ancestry individuals were analyzed. The associations between metabolites and PCa risk were evaluated using the inverse-variance weighted method, supplemented by sensitivity analyses including MR-Egger and MR-PRESSO tests. Additionally, we conducted a phenome-wide MR analysis to assess the potential side effects of targeting the identified metabolites for PCa intervention. Our analysis revealed 107 unique blood metabolites significantly associated with PCa risk, with 43 of these associations consistently replicated using instruments from two independent data sets. This study provides novel insights into the potential role of specific metabolites in the etiology of PCa, which warrants further investigations.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HPV16 CpG Methylation Contributes to Cervical Carcinogenesis by Regulating HPV16 Tumorigenesis-Related Genes. HPV16 CpG甲基化通过调控HPV16肿瘤发生相关基因参与宫颈癌发生

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-15 DOI: 10.1002/mc.23926

Yuanjing Lyu, Meng Cui, Nan Hu, Xiao Zheng, Li Song, Caihong Wu, Ruixin Pei, Ling Ding, Jintao Wang

{"title":"HPV16 CpG Methylation Contributes to Cervical Carcinogenesis by Regulating HPV16 Tumorigenesis-Related Genes.","authors":"Yuanjing Lyu, Meng Cui, Nan Hu, Xiao Zheng, Li Song, Caihong Wu, Ruixin Pei, Ling Ding, Jintao Wang","doi":"10.1002/mc.23926","DOIUrl":"https://doi.org/10.1002/mc.23926","url":null,"abstract":"HPV16 CpG methylation is associated with cervical carcinogenesis and the expression of HPV16 tumorigenesis-related genes. However, the genome-wide methylation profile of HPV16 CpG sites during cervical carcinogenesis has not been fully characterized, and the regulatory role of HPV16 CpG methylation in the expression of these genes in cervical carcinogenesis remains unclear. This study aims to comprehensively map HPV16 CpG methylation patterns across different cervical carcinogenesis stages and elucidate its regulatory effect on the expression of HPV16 tumorigenesis-related genes as well as biological alterations in cervical cancer cells. A total of 341 participants diagnosed with various stages of cervical lesions and normal cervix were enrolled to evaluate the associations between HPV16 CpG methylation, expression of HPV16 tumorigenesis-related genes, and cervical carcinogenesis. Demethylation of HPV16 CpG sites in Caski cells using 5-Aza-dC was performed to assess subsequent changes in the expression of HPV16 tumorigenesis-related genes and cellular biological functions. HPV16 hypermethylation was associated with an increased risk of cervical cancer and precancerous lesions. Thirty-six specific CpG sites across various regions of the HPV16 genome exhibited progressively elevated methylation levels correlating with lesion severity. Effects of HPV16 CpGs methylation on cervical carcinogenesis were partially mediated by HPV16 oncoproteins. Demethylation of HPV16 CpGs significantly suppressed HPV16 oncogene expression, promoted apoptosis, and inhibited proliferation, migration, and invasion in cervical cancer cells. This study provides novel insights into the role of HPV16 CpG methylation in cervical carcinogenesis through the modulation of HPV16 oncogenes. This might represent a promising therapeutic strategy for impeding cervical cancer progression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HSC70 Promotes Breast Cancer Progression via PTEN Autophagic Degradation and PI3K/AKT/mTOR Activation. HSC70通过PTEN自噬降解和PI3K/AKT/mTOR激活促进乳腺癌进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-14 DOI: 10.1002/mc.23931

Zhengqi Wei, Beichen Xie, Xiangrui Meng, Keke Zhang, Hanyu Wei, Yu Gao, Changhua Liang, Hefei Chen

{"title":"HSC70 Promotes Breast Cancer Progression via PTEN Autophagic Degradation and PI3K/AKT/mTOR Activation.","authors":"Zhengqi Wei, Beichen Xie, Xiangrui Meng, Keke Zhang, Hanyu Wei, Yu Gao, Changhua Liang, Hefei Chen","doi":"10.1002/mc.23931","DOIUrl":"https://doi.org/10.1002/mc.23931","url":null,"abstract":"Heat shock cognate protein 70 (HSC70) functions as a molecular chaperone and plays a crucial role in the regulation of intracellular protein modifications that are involved in tumor autophagy. However, its expression and mechanism in breast cancer have not been studied. The expression of HSC70 was verified by TCGA database and breast cancer patient tissue. We established breast cancer cell models and mouse models using knockdown HSC70. The expression and mechanism of HSC70 in breast cancer were investigated by immunocoprecipitation, protein stability, RNA stability, flow cytometry and biogenic analysis. In this study, we found that HSC70 is highly expressed in breast cancer and that high HSC70 expression positive correlated with poor prognosis using TCGA database and patient tissue verification. Subsequent experimental verification demonstrated that HSC70 drives cell cycle progression and promotes proliferation in breast cancer. Further studies revealed that HSC70 significantly promoted the phosphorylation of PI3K, AKT and mTOR but did not affect the total protein levels. Additionally, the AKT agonist SC79 reversed the effects of HSC70 knockdown on proliferation and cell cycle progression of breast cancer cells. Mechanistically, HSC70 reduces the protein stability of PTEN but does not change its mRNA level, suggesting that HSC70 binds to PTEN and promotes its autophagic degradation. More importantly, in vivo experiments demonstrated that HSC70 knockdown results in slower tumor proliferation and growth. In conclusion, HSC70 can bind to PTEN and promote its autophagic degradation, thereby activating the PI3K/AKT/mTOR signaling pathway to promote cell cycle progression and proliferation in breast cancer. These findings suggest that HSC70 may be a feasible target for breast cancer treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CYP4F11, an NRF2 Target Gene, Promotes Hepatocellular Carcinoma Cell Growth. NRF2靶基因CYP4F11促进肝癌细胞生长

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-05-06 DOI: 10.1002/mc.23925

Jinjing Chen, Carlee A Trindl, Haofeng Ye, Dichun Huang, Aikseng Ooi, Joe G N Garcia, Eli Chapman, Donna D Zhang

{"title":"CYP4F11, an NRF2 Target Gene, Promotes Hepatocellular Carcinoma Cell Growth.","authors":"Jinjing Chen, Carlee A Trindl, Haofeng Ye, Dichun Huang, Aikseng Ooi, Joe G N Garcia, Eli Chapman, Donna D Zhang","doi":"10.1002/mc.23925","DOIUrl":"https://doi.org/10.1002/mc.23925","url":null,"abstract":"Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related mortality globally. Current systemic therapies for HCC are limited and often exhibit unsatisfactory efficacy, underscoring the need for novel therapeutic approaches. Nuclear factor erythroid 2-related factor-2 (NRF2), a master transcription factor regulating cellular redox and metabolic homeostasis, is frequently overexpressed in HCC due to mutations in NFE2L2/NRF2 or its negative regulator Kelch-like ECH-associated protein 1 (KEAP1), contributing to tumor progression. In this study, we identify CYP4F11, a member of the Cytochrome P450 family, as a direct target gene of NRF2. CYP4F11, primarily expressed in the liver, is crucial in fatty acid oxidation and eicosanoid metabolism. We demonstrate that CYP4F11 expression is driven by NRF2 and is significantly elevated in HCC patients harboring NFE2L2 gain of function or KEAP1 loss of function mutations. Functionally, CYP4F11 promotes HCC cell growth, and reduced expression of CYP4F11 not only suppresses HCC cell proliferation but also enhances sorafenib-induced HCC cell death. Further, NRF2 inhibition sensitizes HCC to sorafenib through downregulation of CYP4F11. These findings position CYP4F11 as a novel contributor to HCC progression and highlight the potential of targeting the NRF2-CYP4F11 axis for HCC treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0