title: The tumor suppressor p53 regulates autophagosomal and lysosomal biogenesis in lung cancer cells by targeting transcription factor EB.
abstract: The cellular protein degradation system, such as proteasomal or autophagy-lysosomal system plays an important role in the pathogenesis of a variety of human diseases including cancer. Transcription factor EB (TFEB) is a master transcriptional factor in the regulation of autophagy-lysosome pathway (ALP), and it has multiple biological functions including protein degradation, cell homeostasis and cell survival. In the present study we show that the tumor suppressor p53 can regulate TFEB nuclear translocation and activity in lung cancer cells. We found p53 deletion or chemical inhibition of p53 using pifithrin-α could promote the translocation of TFEB from cytoplasm to the nucleus, thus increased the TFEB-mediated lysosomal and autophagosomal biogenesis in lung cancer cells. Moreover, re-expression of p53 could decrease the expression levels of TFEB-targeting genes involved in ALP, and knockdown of TFEB could abolish the effect of p53 on the regulation of ALP gene expression. Taken together, our data indicate that p53 affects ALP through regulating TFEB nuclear translocation in lung cancer cells. Importantly, our study reveals a critical link between two keys factors in tumourigenesis and autophagy, and suggests a potential important role of p53-TFEB signaling axis in lung cancer.
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Zengli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, PR China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Thoracic & Cardiac Surgery, The Second Affiliated Hospital of Soochow University, No.1055, San Xiang Road, Suzhou, Jiangsu 215004, PR China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, PR China.
authors.forename: Delai
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Thoracic & Cardiac Surgery, The Second Affiliated Hospital of Soochow University, No.1055, San Xiang Road, Suzhou, Jiangsu 215004, PR China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qian
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China.
authors.forename: Anyuan
authors.initials: A
authors.lastname: Zhong
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, PR China. Electronic address: zheng.ying@suda.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China. Electronic address: caicunzhou_dr@163.com.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China. Electronic address: shiminhua@163.com.
authors.forename: Minhua
authors.initials: M
authors.lastname: Shi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000071182:Autophagosomes / Q000378:metabolism*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064972:TFEB protein, human; D016159:Tumor Suppressor Protein p53
keywords: Autophagy; Cancer; Lysosome; TFEB; p53