Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
J Biol Chem. 2022 Nov;298(11):102588. doi: 10.1016/j.jbc.2022.102588. Epub 2022 Oct 12.
Cell adhesion molecule CD44v8-10 is associated with tumor ste0mness and malignancy; however, whether CD44v10 alone confers these properties is unknown. Here, we demonstrated that CD44v10 promotes stemness and chemoresistance of triple-negative breast cancers (TNBCs) individually. Next, we identified that genes differentially expressed in response to ectopic expression of CD44v10 are mostly related to glycolysis. Further, we showed that CD44v10 upregulates glucose transporter 1 to facilitate glycolysis by activating the MAPK/ERK and PI3K/AKT signaling pathways. This glycolytic reprogramming induced by CD44v10 contributes to the stem-like properties of TNBC cells and confers resistance to paclitaxel treatment. Notably, we determined that the knockdown of glucose transporter 1 could attenuate the enhanced effects of CD44v10 on glycolysis, stemness, and paclitaxel resistance. Collectively, our findings provide novel insights into the function of CD44v10 in TNBCs and suggest that targeting CD44v10 may contribute to future clinical therapy.
细胞黏附分子 CD44v8-10 与肿瘤干细胞特性和恶性有关；然而，单独的 CD44v10 是否具有这些特性尚不清楚。在这里，我们证明了 CD44v10 单独促进三阴性乳腺癌（TNBC）的干细胞特性和化疗耐药性。接下来，我们发现，在外源表达 CD44v10 时差异表达的基因主要与糖酵解有关。此外，我们表明 CD44v10 通过激活 MAPK/ERK 和 PI3K/AKT 信号通路来上调葡萄糖转运蛋白 1，从而促进糖酵解。CD44v10 引起的这种糖酵解重编程有助于 TNBC 细胞的类干细胞特性，并赋予对紫杉醇治疗的耐药性。值得注意的是，我们确定葡萄糖转运蛋白 1 的敲低可以减弱 CD44v10 对糖酵解、干细胞特性和紫杉醇耐药性的增强作用。总之，我们的研究结果为 CD44v10 在 TNBC 中的功能提供了新的见解，并表明靶向 CD44v10 可能有助于未来的临床治疗。
