1. Collagen XVII promotes dormancy of colorectal cancer cells by activating mTORC2 signaling.
- Author
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Lin J, Zou B, Li H, Wang J, Li S, Cao J, Xie D, and Wang F
- Subjects
- Humans, Cell Line, Tumor, Animals, Proto-Oncogene Proteins c-akt metabolism, Autoantigens metabolism, Mice, Mice, Nude, Cell Proliferation, Mice, Inbred BALB C, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Mechanistic Target of Rapamycin Complex 2 metabolism, Signal Transduction, Non-Fibrillar Collagens metabolism, Non-Fibrillar Collagens genetics, Collagen Type XVII
- Abstract
Tumor dormancy is the underpinning for cancer relapse and chemoresistance, leading to massive cancer-related death in colorectal cancer (CRC). However, our comprehension of the mechanisms dictating tumor dormancy and strategies for eliminating dormant tumor cells remains restricted. In this study, we identified that collagen XVII (COL17A1), a hemidesmosomal transmembrane protein, can promote the dormancy of CRC cells. The upregulation of COL17A1 was observed to prolong quiescence periods and diminish drug susceptibility of CRC cells. Mechanistically, COL17A1 acts as a scaffold, enhancing the crosstalk between mTORC2 and Akt, thereby instigating the mTORC2-mediated dormant signaling. Notably, the activation of mTORC2 is contingent upon the intracellular domain of COL17A1, regardless of its ectodomain shedding. Our findings underscore a pivotal role of the COL17A1-mTORC2 axis in CRC dormancy, suggesting that mTORC2-specific inhibitors may hold therapeutic prospects for the eradication of dormant tumor cells., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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