Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rho-associated kinase (ROCK) has an essential role in governing cell morphology and motility, and increased ROCK activity contributes to cancer cell invasion and metastasis. Burgeoning data suggest that ROCK is also involved in the growth regulation of tumor cells. However, thus far, the molecular mechanisms responsible for ROCK-governed tumor cell growth have not been clearly elucidated. Here we showed that inhibition of ROCK kinase activity, either by a selective ROCK inhibitor Y27632 or by specific ROCK small interfering RNA (siRNA) molecules, attenuated not only motility but also the proliferation of PC3 prostate cancer cells in vitro and in vivo. Importantly, mechanistic investigation revealed that ROCK endowed cancer cells with tumorigenic capability, mainly by targeting c-Myc. ROCK could increase the transcriptional activity of c-Myc by promoting c-Myc protein stability, and ROCK inhibition reduced c-Myc-mediated expression of mRNA targets (such as HSPC111) and microRNA targets (such as miR-17-92 cluster). We provided evidence demonstrating that ROCK1 directly interacted with and phosphorylated c-Myc, resulting in stabilization of the protein and activation of its transcriptional activity. Suppression of ROCK-c-Myc downstream molecules, such as c-Myc-regulated miR-17, also impaired tumor cell growth in vitro and in vivo. In addition, c-Myc was shown to exert a positive feedback regulation on ROCK by increasing RhoA mRNA expression. Therefore, inhibition of ROCK and its stimulated signaling might prove to be a promising strategy for restraining tumor progression in prostate cancer.
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PMID:ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. 2431 11

C-terminal binding protein-2 (CtBP2) is a CtBP-family member which plays a significant role in tumor initiation, progression and response to therapy. However, little has been known about the potential oncobiological role of CtBP2 and its mechanism in human prostate cancer. In this study, we observed the overexpression of CtBP2 in prostate cancer and demonstrated that its expression was closely correlated with several malignant behaviors, e.g., increased serum PSA level, advanced tumor stage (T3), higher Gleason scores and poor outcome. Furthermore, downregulation of CtBP2 expression in prostate cancer PC3 cells could markedly inhibit their proliferation by inducing apoptosis in vitro. Additionally, CtBP2 inhibition could decrease the level of c-Myc and its direct transcriptional target, HSPC111. Taken together, our investigations demonstrated that low-expression of CtBP2 could highly inhibit proliferation of prostate cancer by c-Myc induced signaling, suggesting that targeting CtBP2 may yield a viable anti-tumor strategy by restraining tumor progression in prostate cancer.
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PMID:CtBP2 could promote prostate cancer cell proliferation through c-Myc signaling. 2483 10