title: Ectopic expression of the ATP synthase β subunit on the membrane of PC-3M cells supports its potential role in prostate cancer metastasis.
abstract: Metastatic prostate cancer is associated with high mortality rates. Identification of metastasis-related proteins may facilitate the development of novel therapies for the treatment of metastatic disease. In the present study, we aimed to identify prostate cancer metastasis-associated membrane proteins. We developed a phage-displayed 7-mer peptide library to screen the target peptides that were specifically bound to PC-3M cells with subtractive panning from normal prostate cells and PC-3 prostate cancer cells. A novel short peptide (B04) was found to have high affinity to highly metastatic PC-3M cells. ATP synthase β subunit (ATP5B) was then identified as a binding partner of B04 on the PC-3M cell surface. ATP5B was expressed on the PC-3M cell membrane and on highly malignant human prostate cancer specimens, as shown using multiple methodologies. Furthermore, ATP5B-positive gold particles were detected on the cellular and mitochondrial membranes by immunoelectromicroscopy. These results implied the possibility that ATP5B may translocate from the inner mitochondrial membrane to the outer surface of PC-3M cells. Additional analysis showed that incubation of B04 with PC-3M cells reduced the detection of ATP5B by western blotting and flow cytometry and significantly inhibited the proliferation, invasion and metastasis of PC-3M cells. In conclusion, ATP5B, as a binding partner of a metastasis-related short peptide (B04) on prostate cancer cells, is involved in promoting prostate cancer metastasis. In conclusion, ATP5B may be a promising biomarker and therapeutic target for highly metastatic malignancies.
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Gaiyun
authors.initials: G
authors.lastname: Li
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Pathology, the Second Clinical Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Pathology, the First Clinical Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Dong
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Pathology, Longgang District Central Hospital of Shenzhen, Shenzhen, Guangdong 518116, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yilei
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001681:Biological Assay; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D061505:Cell Surface Display Techniques; D002645:Chickens; D000066630:Ectopic Gene Expression; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D019151:Peptide Library; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: C506526:ATP5F1B protein, human; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D019151:Peptide Library; D025261:Mitochondrial Proton-Translocating ATPases