The selective autophagy substrate p62 serves as a molecular link between autophagy and cancer. Suppression of autophagy causes p62 accumulation and thereby contributes to tumorigenesis. Here we demonstrate that autophagy deficiency promotes cell proliferation and migration through p62-dependent stabilization of the oncogenic transcription factor Twist1. p62 binds to Twist1 and inhibits degradation of Twist1. In mice, p62 up-regulation promotes tumor cell growth and metastasis in a Twist1-dependent manner. Our findings demonstrate that Twist1 is a key downstream effector of p62 in regulation of cell proliferation and migration and suggest that targeting p62-mediated Twist1 stabilization is a promising therapeutic strategy for prevention and treatment of cancer.
机构:
Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R ChinaNanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
Hu, Yuanchang
Yang, Chao
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Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R ChinaNanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
Yang, Chao
Yang, Shikun
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Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R ChinaNanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
Yang, Shikun
Cheng, Feng
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Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R ChinaNanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
Cheng, Feng
Rao, Jianhua
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Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R ChinaNanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
Rao, Jianhua
Wang, Xuehao
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Nanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R ChinaNanjing Med Univ, Chinese Acad Med Sci, Hepatobiliary Liver Transplantat Ctr, Key Lab Living Donor Transplantat,Affiliated Hosp, Nanjing, Jiangsu, Peoples R China
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King Faisal Univ, Community Coll Abqaiq, POB 4000, Al Hasa 31982, Saudi ArabiaKing Faisal Univ, Coll Comp Sci & Informat Technol, POB 4000, Al Hasa 31982, Saudi Arabia
Aldhyani, Theyazn H. H.
Al-Yaari, Mohammed
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King Faisal Univ, Chem Engn Dept, POB 380, Al Hasa 31982, Saudi ArabiaKing Faisal Univ, Coll Comp Sci & Informat Technol, POB 4000, Al Hasa 31982, Saudi Arabia
机构:
Jiangxi Univ Chinese Med, Doctor Class 2021, Nanchang 330000, Jiangxi, Peoples R China
Shanghai Hudong Hosp, Dept Dermatol, Shanghai 200000, Peoples R ChinaJiangxi Univ Chinese Med, Doctor Class 2021, Nanchang 330000, Jiangxi, Peoples R China
Jin, Lei
Deng, Lin
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Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Trauma Surg, Shanghai 200000, Peoples R ChinaJiangxi Univ Chinese Med, Doctor Class 2021, Nanchang 330000, Jiangxi, Peoples R China
Deng, Lin
Wang, Wanchun
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Jiangxi Univ Chinese Med, Affiliated Hosp, Dept Tradit Chinese Med Surg, Nanchang 330000, Jiangxi, Peoples R ChinaJiangxi Univ Chinese Med, Doctor Class 2021, Nanchang 330000, Jiangxi, Peoples R China
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Princess Nourah bint Abdulrahman Univ, Med Educ Dept, Med Coll, Riyadh, Saudi ArabiaPrincess Nourah bint Abdulrahman Univ, Med Educ Dept, Med Coll, Riyadh, Saudi Arabia