AUTHOR=Pradhan Tapas , Kumar Vikas , Surya H Evangeline , Krishna R. , John Samu , Jissa V. T. , Anjana S. , Chandramohan K. , Nair S. Asha 

TITLE=STIL Endows Oncogenic and Stem-Like Attributes to Colorectal Cancer Plausibly by Shh and Wnt Signaling

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.581671

DOI=10.3389/fonc.2021.581671

ISSN=2234-943X

ABSTRACT=<p>The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. <italic>STIL</italic> is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of <italic>STIL</italic> gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). <italic>STIL</italic> silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers <italic>CD133</italic> and <italic>CD44</italic> and drug resistant markers <italic>thymidylate synthase</italic>, <italic>ABCB1</italic>, and <italic>ABCG2</italic> both in <italic>in-vitro</italic> and <italic>in-vivo</italic> CRC models. In addition, high expression of <italic>STIL</italic> mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that <italic>STIL</italic>-mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found <italic>STIL</italic> 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 <italic>STIL</italic>. Our study suggests an instrumental role of <italic>STIL</italic> in molecular manifestation of CRC and progression.</p>