RhoA is associated with invasion and poor prognosis in colorectal cancer

Abstract

Colorectal cancer is one of the most common cancers and is the fourth leading cause of cancer death in Korea. Mortality of colorectal cancer is strongly associated with the metastatic spread of the disease. As such, it is important to find and characterize signaling pathways involved in colon cancer metastasis. We investigated the functional importance of RhoA using human cell lines as well as 150 colorectal cancer patient-derived samples as it remains unclear whether RhoA functions as either an oncogene or a tumor suppressor in colon cancer. RhoA was highly expressed in metastatic cancer cell lines. Although cancer cell proliferation was only moderately impaired after depletion of RhoA, RhoA-depleted cancer cells exhibited markedly reduced migration and invasion ability in vitro. Furthermore, we found that RhoA is associated with the invasion of lymph nodes and blood vessels in the patient colorectal cancer samples. Most notably, patients with higher RhoA expression had a significantly poorer 5-year survival rate after surgery. These results suggest that RhoA is a marker of poor prognosis in colorectal cancer and may be a promising target for cancer treatment.

ILK supports RhoA/ROCK-mediated contractility of human intestinal epithelial crypt cells by inducing the fibrillogenesis of endogenous soluble fibronectin during the spreading process

“…The functional relationship between ILK and FN fibrillogenesis, as observed herein with HIEC, is different from those reported previously with other cell models and constitutes further justification for acquiring a better understanding of the roles of ILK in ECM-integrin-actin interaction dynamicsespecially in the context of intestinal epithelial mechanobiology with regards to homeostasis and disease states. Indeed, our results suggest that ILK can be a particularly interesting target to evaluate for the treatment of intestinal pathologies such as colon cancer and inflammatory bowel diseases since deregulation of fibronectin, integrin α5β1 and RhoA function or expression have been shown to contribute to the progression of colon cancer and poor prognosis [82][83][84], while abnormal assembly of FN can trigger intestinal tumor invasion [85] and excessive collagen deposition associated with the formation of fibrous lesions and tissues fibrosis in inflammatory condition [86,87].…”

Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention

“…RhoA has been shown to regulate tumor progression in several tumors [46–50]. Interestingly, RhoA also regulates radioresistance in glioblastoma, by modulating Survivin activity [51].…”

“…RhoA is shown to be expressed at the tumor front and found to be associated with poor prognosis in prostate cancer [48]. Inhibition of RhoA led to decreased proliferation and migration in gastric cancer cell line [49] and reduced migration in colorectal cancers [50]. Observations suggest that activated RhoA is found in the nucleus upon irradiation of tumor cells [52].…”

Specific role of RhoC in tumor invasion and metastasis

“…A growing number of reports focus on RhoC as an essential factor for invasion and metastasis of various types of tumor cells [ 5 – 9 ], whereas RhoA rather seems to play a role for proliferation instead [ 10 – 12 ]. In colorectal cancer, however, RhoA seems to have low impact on proliferation but is essential for invasion and migration [ 13 ]. Only few studies directly compared the ability of the two closely related Rho GTPases to induce proliferation and invasion [ 14 , 15 ].…”