Kindlin-2 regulates colonic cancer stem-like cells survival and self-renewal via Wnt/β-catenin mediated pathway
Cellular Signalling, ISSN: 0898-6568, Vol: 113, Page: 110953
2024
- 4Citations
- 12Captures
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Metrics Details
- Citations4
- Citation Indexes4
- CrossRef1
- Captures12
- Readers12
- 12
Article Description
Cancer Stem Cells (CSCs) have emerged as a critical mediator in recurrence and resistance in cancers. Kindlin-isoform (1 and 2) binds with cytoplasmic β-tail of integrin and are essential co-activators of integrin function. Given their important function in regulating cancer hallmarks such as cell proliferation, invasion, migration, and metastasis, we hypothesize that it might play a critical role in CSC growth, survival, and self-renewal of colon cancer. Using knockdown approaches, we inhibited Kindlin-2 expression in HCT116 and HT29 colon cancer cells. Extreme limiting dilution and self-renewal assay were performed to measure the role of Kindlin in colonic CSC. Standard methods such as qRT-PCR and western blotting were carried out to understand the signaling cascade by which Kindlin regulates CSC marker expression and downstream targets. Our data show isoform-specific upregulation of Kindlin-2 in colonic CSCs. The silencing of Kindlin-2 reduces colonosphere formation, decreases CSC size, and self-renewal marker genes such as CD-133, CXCR-4, LGR-5, and C-MYC. Kindlin-2 silencing reduces colonosphere proliferation, invasion, and migration of colonic CSCs. Mechanistically, Kindlin-2 silencing reduces the expression, and nuclear localization of β-catenin, and decreases β-catenin target genes such as C-MYC, cyclin D1, DKK-1, and Snail-1. Our study delineates the isoform-specific activity of Kindlin-2 in regulating Colonic CSC. Isoform-specific targeting of Kindlin-2 may be a novel strategy to tackle this devastating disease.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0898656823003686; http://dx.doi.org/10.1016/j.cellsig.2023.110953; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85179638315&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/38084837; https://linkinghub.elsevier.com/retrieve/pii/S0898656823003686; https://dx.doi.org/10.1016/j.cellsig.2023.110953
Elsevier BV
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