title: Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) induces apoptosis in LNCaP prostate cancer cells.
abstract: Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Albert-Str. 25, Freiburg 79104, Germany. gudula.schmidt@pharmakol.uni-freiburg.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Augspach
authors.forename: Joachim H
authors.initials: JH
authors.lastname: List
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
authors.forename: Heike
authors.initials: H
authors.lastname: Bielek
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwan
authors.forename: Ursula
authors.initials: U
authors.lastname: Elsässer-Beile
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
authors.forename: Gudula
authors.initials: G
authors.lastname: Schmidt
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D015007:Yersinia; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; C060296:cytotoxic necrotizing factor type 1; C066737:RHOA protein, human; D009218:Myosins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein