同源盒蛋白纳米
癌症干细胞
癌症研究
刺猬
生物
音猬因子
脱氮酶
细胞生物学
刺猬信号通路
环胺
癌症
胶质1
干细胞
下调和上调
信号转导
胚胎干细胞
基因
泛素
诱导多能干细胞
遗传学
作者
Rongxuan Zhu,Olivier Gires,Lin Zhu,Jun Liu,Junjian Li,Hao Yang,Gaoda Ju,Jing Huang,Weiting Ge,Yi Chen,Zhimin Lu,Hongxia Wang
标识
DOI:10.1038/s41467-019-10739-3
摘要
Abstract Cancer stem cells (CSCs) represent a major source of treatment resistance and tumor progression. However, regulation of CSCs stemness is not entirely understood. Here, we report that TSPAN8 expression is upregulated in breast CSCs, promotes the expression of the stemness gene NANOG, OCT4, and ALDHA1, and correlates with therapeutic resistance. Mechanistically, TSPAN8 interacts with PTCH1 and inhibits the degradation of the SHH/PTCH1 complex through recruitment of deubiquitinating enzyme ATXN3. This results in the translocation of SMO to cilia, downstream gene expression, resistance of CSCs to chemotherapeutic agents, and enhances tumor formation in mice. Accordingly, expression levels of TSPAN8, PTCH1, SHH, and ATXN3 are positively correlated in human breast cancer specimens, and high TSPAN8 and ATXN3 expression levels correlate with poor prognosis. These findings reveal a molecular basis of TSPAN8-enhanced Sonic Hedgehog signaling and highlight a role for TSPAN8 in promoting cancer stemness.
科研通智能强力驱动
Strongly Powered by AbleSci AI