2. Academic Validation
  3. FKBP51 promotes invasion and migration by increasing the autophagic degradation of TIMP3 in clear cell renal cell carcinoma

FKBP51 promotes invasion and migration by increasing the autophagic degradation of TIMP3 in clear cell renal cell carcinoma

  • Cell Death Dis. 2021 Oct 1;12(10):899. doi: 10.1038/s41419-021-04192-8.
Shaowei Mao 1 2,  Di Zhang 3,  Luan Chen 1 3,  Jie Tan 1 3,  Yunpeng Chu 1 3,  Sijia Huang 3,  Wenqi Zhou 1,  Hengwei Qin 4,  Qinghua Xia 5,  Yueran Zhao 5,  Rongxiu Li 1 2,  Shengying Qin  # 6 7,  Muyun Wei  # 8 9
Affiliations

Affiliations

  • 1 School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China.
  • 2 State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China.
  • 3 Bio-X Institutes, Key Laboratory of the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China.
  • 4 School of Medicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China.
  • 5 Shandong Provincial Hospital, 324 Jingwu Road, Jinan, China.
  • 6 School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China. chinsir@sjtu.edu.cn.
  • 7 Bio-X Institutes, Key Laboratory of the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China. chinsir@sjtu.edu.cn.
  • 8 School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China. wmy2940@sjtu.edu.cn.
  • 9 Bio-X Institutes, Key Laboratory of the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China. wmy2940@sjtu.edu.cn.
  • # Contributed equally.
PMID: 34599146 DOI: 10.1038/s41419-021-04192-8
Abstract

The occurrence of metastasis is a serious risk for renal cell carcinoma (RCC) patients. In order to develop novel therapeutic approaches to control the progression of metastatic RCC, it is of urgent need to understand the molecular mechanisms underlying RCC metastasis and identify prognostic markers of metastatic risk. Matrix Metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been known to be closely associated with extracellular matrix (ECM) turnover, which plays a highly active role in tumor metastasis. Recent studies have shown that immunophilin FK-506-binding protein 51 (FKBP51) may be important for the regulation of ECM function, and exert effects on the invasion and migration of tumor cells. However, the mechanisms underlying these activities remain unclear. The present study detected the role of FKBP51 in clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, and found that FKBP51 significantly promotes ccRCC invasion and migration by binding with the TIMP3, connecting TIMP3 with Beclin1 complex and increasing autophagic degradation of TIMP3. Given the important roles that TIMPs/MMPs play in ECM regulation and remodeling, our findings will provide new perspective for future investigation of the regulation of metastasis of kidney Cancer and Other types of Cancer.

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