Cell adhesion molecule CD44v10 promotes stem-like properties in triple-negative breast cancer cells via glucose transporter GLUT1-mediated glycolysis.
Cell adhesion molecule CD44v10 promotes stem-like properties in triple-negative breast cancer cells via glucose transporter GLUT1-mediated glycolysis.
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DOI：
10.1016/j.jbc.2022.102588
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发表时间：
2022-11
影响因子：
4.8
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Guo, Qian;Qiu, Yaqi;Liu, Yiwen;He, Yiqing;Zhang, Guoliang;Du, Yan;Yang, Cuixia;Gao, Feng
细胞粘附分子CD44v8 - 10与肿瘤的坚固性和恶性度相关;然而，CD44v10是否单独赋予这些特性尚不清楚。在这里，我们证明了CD44v10单独促进三阴性乳腺癌（TNBC）的干性和耐药性。接下来，我们确定了响应于CD44v10异位表达的差异表达的基因主要与糖酵解相关。此外，我们发现CD44v10通过激活MAPK/ERK和PI3K/AKT信号通路上调葡萄糖转运蛋白1以促进糖酵解。这种由CD44v10诱导的糖酵解重编程有助于TNBC细胞的干细胞样特性，并赋予对紫杉醇治疗的抗性。值得注意的是，我们确定了敲低葡萄糖转运蛋白1可以减弱CD44v10对糖酵解、干性和紫杉醇耐药性的增强作用。总的来说，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。
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.
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