Xia Yan, Zhang Yin-Li, Yu Chao, Chang Ting, Fan Heng-Yu
Assisted Reproductive Centre, Shaanxi Maternal and Child Care Service Hospital, Xi'an, China; Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
PLoS One. 2014 Nov 4;9(11):e109575. doi: 10.1371/journal.pone.0109575. eCollection 2014.
Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs) and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC) through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical.
近期证据表明,包括卵巢癌在内的一些实体瘤含有不同的干细胞群,这些干细胞群负责肿瘤的起始、生长、化疗耐药及复发。Hippo信号通路已引起广泛关注,一些研究人员聚焦于YAP在维持干性和细胞分化方面的功能。在本研究中,我们成功分离出卵巢癌起始细胞(OCICs),并证明YAP通过其下游共激活因子TEAD促进卵巢癌起始细胞(OCIC)的自我更新。YAP和TEAD家族对于维持可能参与OCICs干性和化疗耐药的特定基因的表达是必需的。综上所述,我们的数据首次表明YAP/TEAD共激活因子调节卵巢癌起始细胞的多能性和化疗耐药性。这提出了一种关于癌症干细胞耐药性的新机制,即Hippo-YAP信号通路可能成为临床卵巢癌治疗的靶点。