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| Content Provider | frontiers |
|---|---|
| Author | Pradhan, Tapas Kumar, Vikas Surya H, Evangeline Krishna, R. John, Samu Jissa, V. T. Anjana, S. Chandramohan, K. Nair, S. Asha |
| Description | Discovery of potent genes regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene, however, its molecular insights and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL 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 & CD44 and drug-resistant markers Thymidylate synthase, ABCB1 & ABCG2 both in in-vitro and in-vivo CRC models. In addition, overexpression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. To our surprise, we observed an Shh independent regulation of stemness and drug-resistant genes mediated by STIL. Interestingly, we found an Shh independent regulation of β-catenin mediated by STIL via p-AKT, which partially answers Shh independent regulatory mechanism of CSC markers by STIL. Our study suggests an instrumental role of STIL in the molecular manifestation of CRC and progression. |
| Abstract | 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. |
| ISSN | 2234943X |
| DOI | 10.3389/fonc.2021.581671 |
| Volume Number | 11 |
| Journal | Frontiers in Oncology |
| Language | English |
| Publisher Date | 2021-08-12 |
| Access Restriction | Open |
| Subject Keyword | Colorectal cancer Cancer stem cell Prognosis STIL Oncogene in CRC drug resistance 2 Drug Resistance STIL Hedgehog signaling Β-catenin |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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