2. Academic Validation
  3. Collagen XVII promotes dormancy of colorectal cancer cells by activating mTORC2 signaling

Collagen XVII promotes dormancy of colorectal cancer cells by activating mTORC2 signaling

  • Cell Signal. 2024 Aug:120:111234. doi: 10.1016/j.cellsig.2024.111234.
Jinlong Lin 1,  Bingxu Zou 1,  Hongbo Li 2,  Jing Wang 3,  Shuman Li 4,  Jinghua Cao 1,  Dan Xie 5,  Fengwei Wang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
  • 2 Department of Musculoskeletal Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
  • 3 Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
  • 4 Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
  • 5 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: xiedan@sysucc.org.cn.
  • 6 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: wangfengw@sysucc.org.cn.
PMID: 38795810 DOI: 10.1016/j.cellsig.2024.111234
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.

Keywords

COL17A1; CRC; Dormancy; Scaffold; mTORC2.

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