Cui Yangyang, Peng Jinghui, Zheng Mingjie, Ge Han, Wu Xiaowei, Xia Yiqin, Huang Yue, Wang Shui, Yin Yongmei, Fu Ziyi, Xie Hui
Department of Breast Surgery, The First Hospital Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Department of Oncology, The First Hospital Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Transl Oncol. 2022 Aug;22:101447. doi: 10.1016/j.tranon.2022.101447. Epub 2022 May 16.
Breast cancer is the most common malignant tumor worldwide and the leading cause of cancer-related deaths in female. Metabolic reprogramming plays critical roles in breast tumorigenesis and induces enhanced glucose uptake and glycolysis. TRPC5OS is encoded by short transient receptor potential channel 5 opposite strand, and predicted to correlate with tumor metabolic reprogramming. Here we aim to elucidate the function of TRPC5OS in aberrant metabolism mediated tumorigenesis. We detected TRPC5OS expression levels in cell lines and tissues by quantitative real-time polymerase chain reaction and immunohistochemistry. Then we assessed the effects of TRPC5OS on proliferation and cell cycle progression in breast cancer cells by cell counting kit-8, colony-formation, EdU-incorporation assays and flow cytometry. Tumor growth in vivo was observed in a mouse xenograft model. Mass spectrum analyses were performed to identify potential interactors of TRPC5OS in tumor cells, and the interaction between TRPC5OS and interactors was validated by co-immunoprecipitation (CO-IP), western blots, and immunofluorescent staining. Glucose uptake was measured by liquid scintillation spectrometry. TRPC5OS highly expresses both in breast tumors and cell lines, and might be an independent prognostic marker for breast cancer patients. Overexpressed TRPC5OS promotes breast cancer cell proliferation, cell cycle progression, and enhances tumor xenograft growth. Mass spectral and CO-IP data showed that TRPC5OS interacts with ENO1. We also demonstrate that TRPC5OS could enhance ENO1/PI3K/Akt-mediated glucose uptake in breast cancer cells. Our study demonstrated that TRPC5OS promotes breast tumorigenesis by ENO1/PI3K/Akt-mediated glucose uptake. TRPC5OS might be an independent prognostic marker and potential therapeutic target for breast cancer patients.
乳腺癌是全球最常见的恶性肿瘤，也是女性癌症相关死亡的主要原因。代谢重编程在乳腺肿瘤发生中起关键作用，并诱导葡萄糖摄取和糖酵解增强。TRPC5OS由瞬时受体电位通道5反向链编码，预计与肿瘤代谢重编程相关。在此，我们旨在阐明TRPC5OS在异常代谢介导的肿瘤发生中的功能。我们通过定量实时聚合酶链反应和免疫组织化学检测了细胞系和组织中TRPC5OS的表达水平。然后，我们通过细胞计数试剂盒-8、集落形成、EdU掺入试验和流式细胞术评估了TRPC5OS对乳腺癌细胞增殖和细胞周期进程的影响。在小鼠异种移植模型中观察体内肿瘤生长。进行质谱分析以鉴定肿瘤细胞中TRPC5OS的潜在相互作用分子，并通过免疫共沉淀（CO-IP）、蛋白质印迹和免疫荧光染色验证TRPC5OS与相互作用分子之间的相互作用。通过液体闪烁光谱法测量葡萄糖摄取。TRPC5OS在乳腺肿瘤和细胞系中均高表达，可能是乳腺癌患者的独立预后标志物。过表达的TRPC5OS促进乳腺癌细胞增殖、细胞周期进程，并增强肿瘤异种移植生长。质谱和CO-IP数据表明TRPC5OS与ENO1相互作用。我们还证明TRPC5OS可以增强ENO1/PI3K/Akt介导的乳腺癌细胞葡萄糖摄取。我们的研究表明，TRPC5OS通过ENO1/PI3K/Akt介导的葡萄糖摄取促进乳腺肿瘤发生。TRPC5OS可能是乳腺癌患者的独立预后标志物和潜在治疗靶点。
