Wnt信号通路
结直肠癌
癌症研究
生物
癌变
癌症干细胞
干细胞
音猬因子
癌症
克拉斯
刺猬
刺猬信号通路
转移
作者
Tapas Pradhan,Vikas Kumar,Evangeline Surya H,R. Krishna,Samu John,V. T. Jissa,S. Anjana,K. Chandramohan,S. Asha Nair
标识
DOI:10.3389/fonc.2021.581671
摘要
The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 and CD44 and drug resistant markers thymidylate synthase, ABCB1, and ABCG2 both in in-vitro and in-vivo CRC models. In addition, high expression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that STIL-mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found STIL regulate β-catenin levels through p-AKT, independent of Shh pathway. This partially answers Shh independent regulatory mechanism of cancer stem cell (CSC) markers by STIL. Our study suggests an instrumental role of STIL in molecular manifestation of CRC and progression.
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