Molecular Carcinogenesis最新文献_第4页

Adipose Secreted Slit2-C Suppresses Breast Cancer Invasion Through cAMP/PKA Transition. 脂肪分泌的Slit2-C通过cAMP/PKA转换抑制乳腺癌侵袭。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-01 DOI: 10.1002/mc.23915

Haolin Hu, Kexuan Li, Lifei Han, Yangyang Gu, Zhenling Ji

{"title":"Adipose Secreted Slit2-C Suppresses Breast Cancer Invasion Through cAMP/PKA Transition.","authors":"Haolin Hu, Kexuan Li, Lifei Han, Yangyang Gu, Zhenling Ji","doi":"10.1002/mc.23915","DOIUrl":"10.1002/mc.23915","url":null,"abstract":"Adipose tissue activation plays a positive role in breast cancer outcomes, consistent with the improved outcomes observed through exercise and weight loss mediated by brown and beige fat. However, the underlying mechanism of this process remains unclear. C-terminal fragment of Slit2 (Slit2-C), endogenously produced by brown or beige adipose cells could increase the thermogenic process of adipose cells in autocrine and paracrine manners. Here, we show that Slit2-C dominantly reduces breast cancer cell invasion through cAMP/PKA mediated inhibition of epithelial-mesenchymal transition. In the process, Slit2-C plays a vital role as a positive regulator of cAMP/PKA signaling in breast cancer. As a result, the overexpression of Slit2-C leads to a reduction in cancer cell invasion and an increase in both the epithelial phenotype and thermogenesis. Besides, inhibiting PKA phosphorylation with H89 reversed the reduced invasion process seen in human breast cancer cells overexpressing Slit2-C, which suggests that the effect of Slit2-C on reducing invasion is mediated through the activation of PKA signaling. Taken together, our study suggests that the modulation of the Slit2-C/cAMP/PKA axis might be a potential targeting therapeutic intervention in aggressive breast cancers.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1149-1159"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764490","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

Differential Response and Resistance to KRAS-Targeted Therapy. kras靶向治疗的差异反应和耐药。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-01 Epub Date: 2025-04-21 DOI: 10.1002/mc.23908

Zhaojin Liu, Heinz-Josef Lenz, Jian Yu, Lin Zhang

{"title":"Differential Response and Resistance to KRAS-Targeted Therapy.","authors":"Zhaojin Liu, Heinz-Josef Lenz, Jian Yu, Lin Zhang","doi":"10.1002/mc.23908","DOIUrl":"10.1002/mc.23908","url":null,"abstract":"KRAS is the most frequently mutated oncogene. In epithelial malignancies such as lung, colorectal, and pancreatic tumors, KRAS is mutated in 25 to above 90% cases. KRAS was considered undruggable for over three decades until the recent development of covalent inhibitors targeting the KRAS G12C mutant. The recent approval of the KRAS G12C inhibitors sotorasib and adagrasib has ushered in a new era of KRAS-targeted therapy. Despite this success, a major challenge in KRAS-targeted therapy is intrinsic and acquired resistance to KRAS inhibitors. Clinical studies have shown that many patients with KRAS G12C cancers did not respond to sotorasib and adagrasib. Colorectal cancer, in particular, has a markedly lower response rate to KRAS G12C inhibitors compared to non-small cell lung cancer. Furthermore, the therapeutic response to KRAS G12C inhibition was short-lived, with quick emergence of acquired resistance. In this review, we summarize several major themes that have emerged from recent clinical and preclinical studies on the mechanisms of intrinsic and acquired resistance to KRAS-targeted therapy in colorectal, lung, and pancreatic cancers. We also discuss various combination strategies for targeting these mechanisms to overcome resistance to KRAS inhibitors.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1135-1148"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971770","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

KIAA1429 and AlkB Homolog 5 Regulate Bladder Cancer Progression via N⁶-Methyladenosine-Dependent Modulation of Sonic Hedgehog Signaling. KIAA1429和AlkB同源物5通过n6 -甲基腺苷依赖的Sonic Hedgehog信号调节膀胱癌的进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-26 DOI: 10.1002/mc.70004

Zhimin Jiao, Xiaowu Liu, Xiaoliang Yuan, Xugang Wang, Qinyu Xu, Haoran Wu

{"title":"KIAA1429 and AlkB Homolog 5 Regulate Bladder Cancer Progression via N6-Methyladenosine-Dependent Modulation of Sonic Hedgehog Signaling.","authors":"Zhimin Jiao, Xiaowu Liu, Xiaoliang Yuan, Xugang Wang, Qinyu Xu, Haoran Wu","doi":"10.1002/mc.70004","DOIUrl":"https://doi.org/10.1002/mc.70004","url":null,"abstract":"N6-methyladenosine (m6A) modification plays a pivotal role in cancer progression, yet its regulatory mechanisms in bladder cancer (BCa) remain poorly understood. This study investigates the functions of two key m6A regulators-α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) and KIAA1429-in modulating BCa cell behavior. Expression levels of ALKBH5, KIAA1429, and Sonic Hedgehog (SHH) were examined in BCa tissues and adjacent normal tissues. Functional assays, including methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR), RNA immunoprecipitation (RIP), and RNA stability assessments, were performed in J82 BCa cells to explore the underlying mechanisms. Results revealed that KIAA1429 was significantly upregulated in BCa and promoted cell proliferation, migration, and invasion by enhancing m6A modification and stabilizing SHH mRNA, leading to activation of the Hedgehog signaling pathway. In contrast, ALKBH5, which was downregulated in BCa, acted as an m6A demethylase that destabilized SHH mRNA and attenuated Hedgehog pathway activity, thereby counteracting the oncogenic effects of KIAA1429. Moreover, overexpression of SHH reversed the inhibitory effects induced by KIAA1429 knockdown, confirming its role as a downstream effector. In conclusion, ALKBH5 and KIAA1429 exert opposing regulatory effects on BCa progression via m6A-mediated modulation of SHH expression and Hedgehog signaling. These findings highlight SHH mRNA methylation as a central mechanism in BCa malignancy and identify ALKBH5 and KIAA1429 as potential therapeutic targets.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497529","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

CDKL3 Targets ATG5 to Exacerbate the Progression of Malignant Melanoma. CDKL3靶向ATG5加速恶性黑色素瘤的进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-26 DOI: 10.1002/mc.70002

Qi Chen, Wenyuan Yu, Yifei Gu, Shikun Cao, Xiaoming Xie, Lijun Wu

{"title":"CDKL3 Targets ATG5 to Exacerbate the Progression of Malignant Melanoma.","authors":"Qi Chen, Wenyuan Yu, Yifei Gu, Shikun Cao, Xiaoming Xie, Lijun Wu","doi":"10.1002/mc.70002","DOIUrl":"https://doi.org/10.1002/mc.70002","url":null,"abstract":"Melanoma is a type of skin cancer originating from melanocytes with a high risk of gastrointestinal tract metastasis. The abnormal expression of cyclin-dependent kinase-like 3 (CDKL3) is involved in several tumor progression. However, the role of CDKL3 in malignant melanoma has never been reported and remains unknown. In this study, the expression of CDKL3 was revealed using clinical human malignant melanoma tissues and normal skin tissues. The effects of CDKL3 on malignant melanoma cell phenotypes was evaluated in vitro and in vivo via establishing CDKL3 deficiency cell models. Our results indicated that CDKL3 was highly expressed in malignant melanoma tissues, especially in advanced malignant melanoma tissues, in comparison with normal skin tissues. Moreover, CDKL3 knockdown significantly suppressed the proliferation, migration and invasion of malignant melanoma cells, and induced cell apoptosis. The indispensable role of CDKL3 on tumorigenesis was confirmed through in vivo experiments. Finally, we showed that CDKL3 promoted malignant melanoma progression via targeting autophagy related 5 (ATG5). CDKL3 induced melanoma cell autophagy through an ATG5-dependent manner. In conclusion, these results showed the promoting role of CDKL3 in proliferation and migration of malignant melanoma cells. The CDKL3 may be a novel biomarker for malignant melanoma progression and the potential therapeutic target for patients with malignant melanoma.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497528","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

M1 Macrophage Extracellular Vesicles and TLR3 Agonist Nanoparticles Down-Regulate Immunosuppression and Metastasis via AKT/TAM in Triple-Negative Breast Cancer. M1巨噬细胞胞外泡和TLR3激动剂纳米颗粒通过AKT/TAM下调三阴性乳腺癌的免疫抑制和转移

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-24 DOI: 10.1002/mc.70003

Shirley V de Paiva Souza, Andreza Conceição Veras Aguiar, Elizabeth Costa S de Albuquerque, Christina Eich, Luis J Cruz, Pablo Lara, Carla Jorquera-Cordero, Raelle Ferreira Gomes, Regina Célia Monteiro de Paula, Rosemayre S Freire, de Araújo Júnior Raimundo Fernandes de AraújoJúnior

{"title":"M1 Macrophage Extracellular Vesicles and TLR3 Agonist Nanoparticles Down-Regulate Immunosuppression and Metastasis via AKT/TAM in Triple-Negative Breast Cancer.","authors":"Shirley V de Paiva Souza, Andreza Conceição Veras Aguiar, Elizabeth Costa S de Albuquerque, Christina Eich, Luis J Cruz, Pablo Lara, Carla Jorquera-Cordero, Raelle Ferreira Gomes, Regina Célia Monteiro de Paula, Rosemayre S Freire, de Araújo Júnior Raimundo Fernandes de AraújoJúnior","doi":"10.1002/mc.70003","DOIUrl":"https://doi.org/10.1002/mc.70003","url":null,"abstract":"Metastasis induced by tumor immune escape has been implicated as one of the factors contributing to the aggressiveness of triple-negative breast cancer. Macrophage type 1-derived extracellular vesicles were isolated and combined with PLGA nanoparticles loaded with the TLR3 agonist poly I:C as a therapeutic strategy to investigate their antitumor activity by downregulating tumor immune escape in the tumor microenvironment (TME) of breast cancer in a murine model of orthotopic tumor growth. Tumors were evaluated by qRT-PCR and immunohistochemistry. Cellular uptake and polarization of murine macrophages (RAW 264.7 cells) were analyzed In Vitro by immunofluorescence and flow cytometry, respectively. Furthermore, mouse survival, lymph node involvement, and metastasis were also evaluated. In the animal model, the combination therapy inhibited tumor progression through TME immunomodulation, leading to a reduction in primary tumor size (p < 0.0001) and metastasis, along with an extension in survival of 11 days. Importantly, both innate and adaptive immune responses were enhanced, as indicated by increased CD8 expression (p < 0.0001) and reduced PD-L1 levels in the TME, as well as elevated CD11c expression in lymph nodes (p < 0.0001). Likewise, the combination therapy suppressed tumor progression by reducing AKT1 expression (p < 0.001) and increasing E-cadherin expression (p < 0.01). Based on these findings, the combination therapy functioned as a \"vaccine-like immunomodulatory strategy,\" promoting TME immunomodulation and suppressing metastasis in a murine model of triple-negative breast cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476105","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

Mitochondrial Energy Metabolic Reprogramming Facilitates the Malignant Progression of Intrahepatic Cholangiocarcinoma. 线粒体能量代谢重编程促进肝内胆管癌的恶性进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-22 DOI: 10.1002/mc.23930

Jun-Long Wang, Yu-Chen Pei, Qi-Zhi Liang, Xi Yu, Jia-Yi Cai, Nian-Dong Yi, Wei-Gen Wu, Yu-Ze Wang, Qi Liu, Wei Chen

{"title":"Mitochondrial Energy Metabolic Reprogramming Facilitates the Malignant Progression of Intrahepatic Cholangiocarcinoma.","authors":"Jun-Long Wang, Yu-Chen Pei, Qi-Zhi Liang, Xi Yu, Jia-Yi Cai, Nian-Dong Yi, Wei-Gen Wu, Yu-Ze Wang, Qi Liu, Wei Chen","doi":"10.1002/mc.23930","DOIUrl":"https://doi.org/10.1002/mc.23930","url":null,"abstract":"Mitochondrial function plays a crucial role in cancer development, with mitochondrial energy metabolism-related genes (MEMRGs) contributing to carcinogenesis. This study investigates the role of MEMRGs in intrahepatic cholangiocarcinoma (ICC) by analyzing RNA-seq data from TCGA and GEO databases to identify differentially expressed MEMRGs. Functional enrichment and KEGG pathway analyses revealed their significant involvement in metabolic pathways. Using weighted gene co-expression network analysis (WGCNA) and consensus clustering, two distinct ICC subtypes were identified. Tumor mutational burden (TMB), immune cell infiltration, and immune escape potential were assessed, highlighting the importance of the Hippo/YAP pathway. Cox regression analyses pinpointed key prognostic genes, including ADH1A, ADH1B, and CYP4A11. A MEMRG-based nomogram was developed that accurately predicted 1- and 3-year survival outcomes. Experimental validation showed that ADH1B suppresses ICC malignancy through the Hippo/YAP pathway. These findings suggest that MEMRGs are vital in ICC progression and immune regulation, serving as promising prognostic biomarkers and therapeutic targets, though further validation is required.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369089","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

Spatial Transcriptomic Landscape of Canine Oral Squamous Cell Carcinoma. 犬口腔鳞状细胞癌的空间转录组学研究。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-17 DOI: 10.1002/mc.23932

Stephanie Goldschmidt, Clifford G Tepper, Jack Goon, Maria Soltero-Rivera, Robert Rebhun, Andrew C Birkeland, Xiao-Jing Wang, Ryan R Davis, Stephenie Y Liu, Iris Rivas, Brian Murphy, Natalis Vapniarsky

{"title":"Spatial Transcriptomic Landscape of Canine Oral Squamous Cell Carcinoma.","authors":"Stephanie Goldschmidt, Clifford G Tepper, Jack Goon, Maria Soltero-Rivera, Robert Rebhun, Andrew C Birkeland, Xiao-Jing Wang, Ryan R Davis, Stephenie Y Liu, Iris Rivas, Brian Murphy, Natalis Vapniarsky","doi":"10.1002/mc.23932","DOIUrl":"https://doi.org/10.1002/mc.23932","url":null,"abstract":"Canine oral squamous cell carcinoma (COSCC) is the second most common oral tumor in dogs and the most relevant for comparative human trials as a spontaneous large animal model of disease. Historical genomic work has focused primarily on bulk sequencing. The present study describes the complete transcriptomic landscape of COSCC with spatial distinction between the surface tumor, deep invasive tumor, peritumoral dysplastic epithelium, and tumor microenvironment compared to matched normal oral samples. Each region demonstrated distinct molecular signatures. Genes related to epithelial growth factor (EGFR) and epithelial-mesenchymal transformation (EMT) were upregulated in both peritumoral dysplasia and surface cancer. Additionally, the KRAS gene set, KRT17, and SSP1 were enriched in cancer. We identified five genes that represent dysplastic lesion with high potential for malignant transformation (FZD4, GAS1, HACD2, NOG, and SLC39A6). Also, three genes, SFRP4, FZD1, and IL34 represented a specific signature of the invasive portion of the COSCC that should be explored for prognostic value as a biomarker of malignancy. Lastly, we verified the immunomodulatory tumor microenvironment detecting an increase in macrophages and an abundance of IL-10 secretion. The other predominant leukocytes were T-cells, with CD4+ T-cells being the most prevalent. CD4+ T cells expressed transcripts for both stimulatory (Inducible T-cell Co-Stimulator (ICOS) and inhibitory molecules (CTLA4). The observed high CTLA4 suggests that this inhibitory signal may be preventing a robust antitumor immune response. Taken together, this study identified multiple targets to be explored for biomarkers of malignancy, prediction of tumor behavior, and potential targets for development of novel therapies.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317512","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

C1QBP Promotes Prostate Cancer Progression and Lipid Accumulation by Negatively Regulating ALDH9A1. C1QBP通过负调控ALDH9A1促进前列腺癌进展和脂质积累。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23904

Xinyu Liu, Jiaxin Li, Runxuan Du, Qiufang Qiao, Shuang Liu, Zhihao Bo, Ruibing Chen, Yihan Dong, Xuesong Xiao, Yuejing Pan, Huamao Jiang, Rui Wang, Yong Wang, Dan Yue

{"title":"C1QBP Promotes Prostate Cancer Progression and Lipid Accumulation by Negatively Regulating ALDH9A1.","authors":"Xinyu Liu, Jiaxin Li, Runxuan Du, Qiufang Qiao, Shuang Liu, Zhihao Bo, Ruibing Chen, Yihan Dong, Xuesong Xiao, Yuejing Pan, Huamao Jiang, Rui Wang, Yong Wang, Dan Yue","doi":"10.1002/mc.23904","DOIUrl":"10.1002/mc.23904","url":null,"abstract":"Prostate cancer (PCa) relies heavily on lipid metabolism for energy acquisition, and lipid metabolic reprogramming plays a crucial role in its progression. Here, we utilized publicly available PCa databases and immunohistochemistry to evaluate C1QBP expression in PCa. We found that C1QBP is highly expressed in PCa, potentially due to promoter hypomethylation. Functional assays showed that C1QBP promotes cell proliferation, migration, and lipid accumulation in PCa cells. We identified differentially expressed proteins associated with C1QBP by using liquid chromatography-tandem mass spectrometry. Functional enrichment analysis revealed that C1QBP affects lipid metabolism and negatively regulates the lipid metabolism-related molecule ALDH9A1. Furthermore, ALDH9A1 intervention rescued the tumor suppression and lipid reduction caused by C1QBP knockdown. RNA sequencing (RNA-seq) was performed to explore C1QBP regulatory pathways at the mRNA level, revealing that C1QBP also affects the MAPK and p53 pathways, as well as the expression of lipid metabolism-related molecules. In conclusion, these findings suggest that C1QBP influences PCa progression and lipid deposition by regulating ALDH9A1, while other potential mechanisms may also be involved, indicating that C1QBP is a promising target for PCa treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"997-1012"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657751","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

CtBP2 Regulates Wnt Signal Through EGR1 to Influence the Proliferation and Apoptosis of DLBCL Cells. CtBP2通过EGR1调控Wnt信号影响DLBCL细胞的增殖和凋亡

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1002/mc.23901

Jianfang Dong, Lihua Li, Xuefei Zhang, Xijing Yin, Zucong Chen

{"title":"CtBP2 Regulates Wnt Signal Through EGR1 to Influence the Proliferation and Apoptosis of DLBCL Cells.","authors":"Jianfang Dong, Lihua Li, Xuefei Zhang, Xijing Yin, Zucong Chen","doi":"10.1002/mc.23901","DOIUrl":"10.1002/mc.23901","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of lymphoma. The overexpression of CtBP2 in tissues may contribute to tumor occurrence and progression. The expression of EGR1 in DLBCL is elevated, suggesting its potential role as an oncogene that promotes the proliferation of DLBCL cells. Database predictions indicate that CtBP2 can bind to EGR1. The objective of the present study was to investigate whether CtBP2 can influence the proliferation and apoptosis of DLBCL cells by regulating the Wnt signaling pathway through EGR1. Western blot assay showed that CtBP2 expression was upregulated in DLBCL cells. Cell proliferation level was detected by CCK8 assay and EdU staining, and the apoptosis level and cycle distribution were analyzed through flow cytometry. Our data indicated that interference with CtBP2 and EGR1 can inhibit the proliferation and cell cycle progression of DLBCL cells while promoting apoptosis. The predictions from the HDOCK server, along with the results of Co-IP experiments, suggested that EGR1 and CtBP2 can effectively bind to each other, with EGR1 positioned downstream of CtBP2 and regulated by it. Furthermore, interference with CtBP2 could also inhibit the expression of the Wnt/β-catenin signaling pathway. Overexpression of EGR1 counteracted the effects of siRNA-CtBP2, promoting cell proliferation and cycle, inhibiting apoptosis and upregulating the expression of the Wnt/β-catenin signaling pathway. From the above experiments, we found that CtBP2 can regulate the Wnt/β-catenin signaling pathway through EGR1 to influence the proliferation and apoptosis of DLBCL cells. Therefore, EGR1 may be one of the key contributors involved in the regulation of Wnt/β-catenin signaling by CtBP2.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"959-969"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657754","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

TSPAN31 Activates Fatty Acid Metabolism and PI3K/AKT Pathway to Promote Tumor Progression in Breast Cancer. TSPAN31激活脂肪酸代谢和PI3K/AKT通路促进乳腺癌肿瘤进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1002/mc.23912

Wenquan Luo, Yuxiang Sun, Liang Cao

{"title":"TSPAN31 Activates Fatty Acid Metabolism and PI3K/AKT Pathway to Promote Tumor Progression in Breast Cancer.","authors":"Wenquan Luo, Yuxiang Sun, Liang Cao","doi":"10.1002/mc.23912","DOIUrl":"10.1002/mc.23912","url":null,"abstract":"Breast cancer (BC) is one of the most common human malignancies, but the mechanisms of BC have not been fully elucidated. Recently, tetraspanin 31 (TSPAN31) is reported to be linked to cancer progression. However, the function of TSPAN31 remains unclear in BC. Investigation of the function and potential mechanism of TSPAN31 in BC was the purpose of this study. Immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were applied to measure TSPAN31 expression. Loss and gain functional experiments were utilized to survey the influences of TSPAN31 on BC biological process, including cell growth, invasion, migration, and fatty acid metabolism. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis based on DepMap database and Gene Set Enrichment Analysis based on The Cancer Genome Atlas database were executed to find TSPAN31-related pathway. Western blot was carried out to assess the changes of fatty acid synthase (FASN), sterol regulatory element binding protein 1 (SREBP1), acyl-CoA synthetase long-chain family member 1 (ACSL1), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K, protein kinase B (AKT), and p-AKT. In human non-triple negative breast cancer tissues and cells, TSPAN31 expression was upregulated. TSPAN31 knockdown induced BC cell apoptosis, inhibited cell proliferation, invasion, migration, and fatty acid metabolism, and reduced the protein levels of FASN, SREBP1, ACSL1, p-PI3K/PI3K, and p-AKT/AKT. In contrast, TSPAN31 overexpression led to the opposite results. Additionally, the activator of PI3K (740 Y-P) attenuated the inhibition of TSPAN31 knockdown on fatty acid metabolism, proliferation, and invasion in BC cells. Through activation of fatty acid metabolism and PI3K/AKT pathway, TSPAN31 played a carcinogenic role in BC. For the mechanism of BC tumorigenesis, our study provides an interesting insight.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1078-1089"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710803","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