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.

Bacterial Toxins and Targeted Brain Therapy: New Insights from Cytotoxic Necrotizing Factor 1 (CNF1)

“…Therefore, it is interesting to investigate the effect that CNF1 can exert on the main events of tumor development. Two crucial aspects of that process are represented by apoptosis and the regulation of actin cytoskeleton [ 48 ]. The effect of CNF1 on apoptosis is still debated.…”

The actin and Rho-modifying toxins PTC3 and PTC5 ofPhotorhabdus luminescens: enzyme characterization and induction of MAL/SRF-dependent transcription

“…All data are given as mean ± SD (n ≥ 3) and significance was tested by using the Student's t-test (*P < 0.05, **P < 0.01, ***P < 0.001; ns, not significant). triggers a negative feedback mechanism resulting in blockade of the activity state of Rho (Reipschläger et al, 2012;Augspach et al, 2013). As shown by the immunoblots, this effect was apparently not caused by degradation of Rho.…”

“…In contrast, activation of Rho by PTC5 was maximal after 4 h and remained increased for at least 18 h. Interestingly, the transient effect of CNF1 was dominant in the presence of both toxins. This finding supports our previous hypothesis that CNF1‐induced activation of Rho subfamily proteins triggers a negative feedback mechanism resulting in blockade of the activity state of Rho (Reipschläger et al ., ; Augspach et al ., ). As shown by the immunoblots, this effect was apparently not caused by degradation of Rho.…”

The role of RhoA in vulvar squamous cell carcinoma: a carcinogenesis, progression, and target therapy marker

“…For example, RhoA depletion diminishes motility, invasion [13,14], and proliferation [15] and increases apoptosis [16,17]. It has been reported that RhoA expression is an independent prognostic factor in gastric cancer, especially diffuse-type gastric cancer [18].…”