The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer

Abstract

ΔROCKII vs. 18.4±1.4 control, p<0.001). Similarly, both exhibited reduced motility compared with control cells (p<0.001) and lost their response to HGF. Importantly, no significant difference existed between knockdown and control cells in in vivo tumour growth. ROCKI was significantly higher in human mammary tumours than normal background tissue (2.9±1.1 vs. 0.29±0.13, p=0.023), although expression of ROCKII was fairly consistent in both (2050±646 vs. 2303±2079). ROCKI expression was greater in patients who died from breast cancer than in patients who remained disease free (11.6±7.1 vs. 1.95±0.95). Higher levels of ROCKI were associated with increased grade (0.95±0.73 grade-1; 2.11±1.72 grade-2; and 4.06±1.99 grade-3). Levels of ROCKI, but not ROCKII, were significantly correlated with overall survival of patients (p=0.004, Univariate analysis, median follow-up 120 month).These results show that ROCKI and possibly ROCKII are key factors in regulation of motility/invasion of breast cancer cells. This, together with significant correlation between ROCKI and poor outcome in clinical breast cancer, indicates that it is a potential target in human breast cancer.

Combined inhibition of rho-associated protein kinase and EGFR suppresses the invasive phenotype in EGFR-dependent lung cancer cells

“…Overexpression of the ROCK proteins has been implicated in the invasive and metastatic potential of various tumor types [9][10][11]. Baseline protein expression of ROCK1 and ROCK2 was higher in H1975 cells compared to H1650 and H358 NSCLC cells (Fig.…”

Actin-bundling proteins in cancer progression at a glance

“…Phosphorylation of the myosin II light chain triggers the contractile activity of myosin II (Narumiya et al, 2009). High levels of the myosin kinase Rho-associated protein kinase 1 (ROCK1) are associated with poor survival in breast cancer patients (Lane et al, 2008) and correlate with poor tumour differentiation, muscle invasion and lymph node metastasis in bladder cancer (Kamai et al, 2003). One clinical study showed a positive correlation between myosin light chain kinase, which activates myosin II, with disease recurrence and metastasis in non-small cell lung cancer (Minamiya et al, 2005).…”

Inhibition of Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone

“…ROCK is implicated in the regulation of breast cancer metastasis. A clinical study showed that increased expression of ROCK corresponds to late-stage tumors and metastases and is negatively correlated with overall survival in breast cancer patients (1). Overexpression of ROCK enhances invasion/migration in breast and other tumor cells in vitro (2,3).…”