title: Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration.
abstract: Impaired expression of connexins, the gap junction subunits that facilitate direct cell-cell communication, have been implicated in prostate cancer growth. To elucidate the crucial role of connexins in prostate cancer progression, we performed a systematic quantitative RT-PCR screening of connexin expression in four representative prostate cancer cell lines across the spectrum of malignancy. Transcripts of several connexin subunits were detected in all four cell lines, and connexin 43 (Cx43) showed marked elevation at both RNA and protein levels in cells with increased metastatic potential. Analysis of gap-junction-mediated intercellular communication revealed homocellular coupling in PC-3 cells, which had the highest C x 43 expression, with minimal coupling in LNCaP cells where C x 43 expression was very low. Treatment with the gap junction inhibitor carbenoxolone or connexin mimetic peptide ACT-1 did not impair cell growth, suggesting that growth is independent of functional gap junctions. PC-3 cells with C x 43 expression reduced by shRNA showed decreased migration in monolayer wound healing assay, as well as decreased transwell invasion capacities when compared to control cells expressing non-targeting shRNA. These results, together with the correlation between C x 43 expression levels and the metastatic capacity of the cell lines, suggest a role of C x 43 in prostate cancer invasion and metastasis.
authors.affiliation: Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, 44195, USA.|Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, 44195, USA.|Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hitomi
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Bar-Shain
authors.affiliation: Genitourinary Program, Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo NY, 14263, USA.
authors.forename: Zafardjan
authors.initials: Z
authors.lastname: Dalimov
authors.affiliation: Genitourinary Program, Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo NY, 14263, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Ellis
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, 61656, USA.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Velpula
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH, 44242, USA.
authors.forename: Gail C
authors.initials: GC
authors.lastname: Fraizer
authors.affiliation: Center for Heart and Regenerative Medicine, Virginia Tech Carilion Research Institute, Roanoke, VA, 24016, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gourdie
authors.affiliation: Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, 44195, USA.|Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.|Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; C543076:GJA1 protein, mouse; D012333:RNA, Messenger
keywords: Cx43; gap junction independent function; invasion; prostate cancer