title: Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer.
abstract: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Breast Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Hao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Tu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wei
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D063154:Mitochondrial Dynamics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010085:Oxidative Phosphorylation; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human
keywords: TRAP1; breast cancer; metastasis; mitochondria; tumorigenesis