Rho-Associated Protein Kinase (ROCK) Promotes Proliferation and Migration of PC-3 and DU145 Prostate Cancer Cells by Targeting LIM Kinase 1 (LIMK1) and Matrix Metalloproteinase-2 (MMP-2)

Abstract

Background In the pathogenesis and progression of prostate cancer, cell proliferation and cell migration results in tumor invasion and metastasis that is associated with patient morbidity and mortality. Rho-associated protein kinase (ROCK) has previously been shown to be upregulated in prostate cancer, but its biological role remains poorly understood. This study aimed to investigate the role of ROCK in the proliferation and migration of PC-3 and DU145 prostate cancer cells and to identify the possible targets involved by knockdown of ROCK1 and ROCK2 RNA expression. Material/Methods An RNA interference (RNAi) assay was performed to silence the expression of ROCK1 and ROCK2 in the PC-3 and DU145 human prostate cancer cell lines. Cells were also treated with a specific ROCK inhibitor, Y27632. A cell counting kit-8 (CCK-8) assay was used to determine the proliferation rate of prostate cancer cells, and cell migration and invasion assays were performed. Western blot and polymerase chain reaction were used to measure protein and RNA expression levels. Results In PC-3 and DU145 prostate cancer cells, knockdown of ROCK1 and ROCK2 reduced cell migration and invasion. ROCK1 and ROCK2 regulated cell proliferation in PC-3 and DU145 prostate cancer cells. Protein levels of phosphorylated LIM kinase 1 (p-LIMK1) and matrix metalloproteinase-2 (MMP-2) were reduced in ROCK1 and ROCK2 siRNA transfected cells. Conclusions In PC-3 and DU145 human prostate cancer cells, ROCK promoted cell proliferation and migration by targeting LIMK1 and MMP-2.

Phosphoinositide‐dependent Kinase‐1 (PDPK1) regulates serum/glucocorticoid‐regulated Kinase 3 (SGK3) for prostate cancer cell survival

“…Among them include a number of proto‐oncogene ( ERBB3 , ERBB4 , RET , SRC and YES1 ), pro‐survival genes involved in the PI3K signalling ( AKT1 , AKT3 , GSK3A , GSK3B , PDPK1 and SGK3 ) and MAPK signalling ( MAP3K4 , MAPK1 , MAPK4 , MAPK13 and MAPK15 ). Importantly, knock‐down of AKT1, 27‐29 AKT3, 27‐29 GSK3A, 30‐32 GSK3B, 30‐35 MAPK1 (also known as ERK2), 36,37 MAPK4 (also known as ERK4) 29 and ROCK2 38‐40 have been shown to inhibit PCa cell growth, independently validated our results.…”

“…To identify genes and pathways that modify PCa growth, we con- and MAPK15). Importantly, knock-down of AKT1, [27][28][29] AKT3, [27][28][29] GSK3A, [30][31][32] GSK3B, [30][31][32][33][34][35] MAPK1 (also known as ERK2), 36,37 MAPK4 (also known as ERK4) 29 and ROCK2 [38][39][40] have been shown to inhibit PCa cell growth, independently validated our results. Figure 1D).…”

“…In this study, we identified 45 kinases that mediate PCa cell survival. These include previously identified proto‐oncogene such as ERBB3 , ERBB4 , RET , SRC and YES1 ; and pro‐survival genes involved in the PI3K and MAPK signalling such as AKT1 , AKT3 , GSK3A , GSK3B , PDPK1 , SGK3 , MAP3K4 , MAPK1 (also known as ERK2 ), MAPK4 (also known as ERK4 ), MAPK13 , MAPK15 and ROCK2 27‐40 . Particularly, knock‐down of PDPK1 induced tumour‐specific cell death in both DU145 and PC3 AR‐negative cells, but not in the AR‐positive LNCaP cells nor in the RWPE‐1 non‐transformed prostate epithelial cells.…”

The Impact of Ang-(1-9) and Ang-(3-7) on the Biological Properties of Prostate Cancer Cells by Modulation of Inflammatory and Steroidogenesis Pathway Genes

“…Higher levels of ROCK1 were associated with prostate tumor stage, and Gleason grade, positive nodal stage, and poor prognosis [ 22 , 23 ]. The knockdown of rho as sociated protein kinase genes (ROCK) reduced the migration and invasion of PC3 and DU-145 cells in vitro, and promoted metastasis in a mouse model in vivo [ 24 ]. Interestingly, pharmacological inhibitors of the Rho pathway reportedly block angiogenesis.…”

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

“…These studies are in line with the fact that dynamic and complex molecular pathways are involved in Pca malignancy [ 32 ]. Some of them are oncogene factors participating in increasing progression and malignancy of cancer cells, while others are onco-suppressor factors that can be regulated in the treatment of PCa [ 33 , 34 , 35 , 36 ]. The result of revealing the role of these pathways is an opportunity for the development of anti-tumor compounds in PCa therapy as confirmed by onco-suppressor studies [ 37 ].…”