Department of Oncology, Shangqiu First people's Hospital, Shangqiu 476100, Henan Province, PR China.
Department of Obstetrics, Zhengzhou Yihe Hospital, Zhengzhou 450003, Henan Province, PR China.
Biomed Pharmacother. 2017 Nov;95:789-794. doi: 10.1016/j.biopha.2017.08.091. Epub 2017 Sep 10.
Altered energy metabolism is a universal property of most cancer cells. The Hippo signaling pathway and its principal downstream effector YAP1 are responsible for tissue homeostasis including organ size, cell proliferation, apoptosis, and differentiation. Dysregulation of the Hippo pathway leads to the activation of YAP1 and further culminates in the development of multiple human cancers. In this study, by loss-of-function assay, we demonstrated that YAP1 contributed to the glycolytic phenotype of breast cancer cells. Knockdown of YAP1 inhibited the extracellular acidification rates, glucose consumption, and lactate production of breast cancer cells. Moreover, YAP1 interacted with TEAD1, exerted their transcriptional control of the functional target, glucose transporter 1 (Glut1). Overexpression of Glut1 restored the inhibitory effects of YAP1 knockdown on glycolysis as demonstrated by glucose consumption and lactate production. Suppression of glycolysis by deprivation of glucose largely compromised the oncogenic roles of YAP1 on cell proliferation, apoptosis, and invasive potential. Taken together, our data identify a novel role of YAP1-TEAD1 pathway in cancer energy metabolism.
能量代谢改变是大多数癌细胞的普遍特征。Hippo 信号通路及其主要下游效应因子 YAP1 负责组织稳态，包括器官大小、细胞增殖、凋亡和分化。Hippo 通路的失调导致 YAP1 的激活，并进一步导致多种人类癌症的发展。在这项研究中，通过功能丧失实验，我们证明 YAP1 促进了乳腺癌细胞的糖酵解表型。YAP1 的敲低抑制了乳腺癌细胞的细胞外酸化率、葡萄糖消耗和乳酸生成。此外，YAP1 与 TEAD1 相互作用，发挥其对葡萄糖转运蛋白 1（Glut1）的功能靶基因的转录调控作用。Glut1 的过表达恢复了 YAP1 敲低对糖酵解的抑制作用，如葡萄糖消耗和乳酸生成所证明的那样。剥夺葡萄糖对糖酵解的抑制在很大程度上削弱了 YAP1 对细胞增殖、凋亡和侵袭潜能的致癌作用。总之，我们的数据确定了 YAP1-TEAD1 通路在癌症能量代谢中的新作用。
