title: Fas-associated protein with death domain (FADD) regulates autophagy through promoting the expression of Ras homolog enriched in brain (Rheb) in human breast adenocarcinoma cells.
abstract: FADD (Fas-associated protein with death domain) is a classical adaptor protein in apoptosis. Increasing evidences have shown that FADD is also implicated in cell cycle progression, proliferation and tumorigenesis. The role of FADD in cancer remains largely unexplored. In this study, In Silico Analysis using Oncomine and Kaplan Meier plotter revealed that FADD is significantly up-regulated in breast cancer tissues and closely associated with a poor prognosis in patients with breast cancer. To better understanding the FADD functions in breast cancer, we performed proteomics analysis by LC-MS/MS detection and found that Rheb-mTORC1 pathway was dysregulated in MCF-7 cells when FADD knockdown. The mTORC1 pathway is a key regulator in many processes, including cell growth, metabolism and autophagy. Here, FADD interference down-regulated Rheb expression and repressed mTORC1 activity in breast cancer cell lines. The autophagy was induced by FADD deficiency in MCF7 or MDA-231 cells but rescued by recovering Rheb expression. Similarly, growth defect in FADD-knockdown cells was also restored by Rheb overexpression. These findings implied a novel role of FADD in tumor progression via Rheb-mTORC1 pathway in breast cancer.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Liangqiang
authors.initials: L
authors.lastname: He
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Yueyang
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, 213164, Jiangsu, China.
authors.forename: Shengwen
authors.initials: S
authors.lastname: Guan
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Dianhua
authors.initials: D
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China.|Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, 213164, Jiangsu, China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001343:Autophagy / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D053200:Fas-Associated Death Domain Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D000076205:Ras Homolog Enriched in Brain Protein / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D000076222:Mechanistic Target of Rapamycin Complex 1
keywords: FADD; Rheb; autophagy; breast cancer; tumorigenesis