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Toxins 2013, 5(11), 2241-2257;

Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Albert-Str. 25, Freiburg 79104, Germany
Klinik für Urologie, Universitätsklinikum Freiburg, Engesser Str. 4b, Freiburg 79108, Germany
Author to whom correspondence should be addressed.
Received: 4 September 2013 / Revised: 1 November 2013 / Accepted: 5 November 2013 / Published: 21 November 2013
(This article belongs to the Special Issue Cytotoxic Necrotizing Factors)
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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. View Full-Text
Keywords: CNFy; apoptosis; prostate cancer; Rho-GTPases CNFy; apoptosis; prostate cancer; Rho-GTPases

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Augspach, A.; List, J.H.; Wolf, P.; Bielek, H.; Schwan, C.; Elsässer-Beile, U.; Aktories, K.; Schmidt, G. Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells. Toxins 2013, 5, 2241-2257.

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