Regulation of colon cancer cell migration and invasion by CLIC1-mediated RVD

Abstract

The metastasis of colorectal cancer is one of the most common causes of death in the world. In this investigation, we used the human colon cancer cell lines LOVO and HT29 as model systems to determine the role of the chloride intracellular channel 1 (CLIC1) in the metastasis of colonic cancer. In the present study, we found that regulatory volume decrease (RVD) capacity was markedly up-regulated in LOVO cells, which are characterized by a high metastatic potential. Functionally suppressing CLIC1 using the specific chloride intracellular channel 1 blocker Indanyloxyacetic acid 94 inhibited RVD and decreased the migration and invasion of colon cancer cells. Moreover, these effects occurred in a dose-dependent manner. The migration and invasion abilities in two cell lines also were inhibited by the knockdown of CLIC1 using small interfering RNA transfection. The mRNA and protein expression of CLIC1 is up-regulated in LOVO cells. In human colon cancer cells, CLIC1 is primarily located in the plasma membrane, where it functions as a chloride channel. Taken together, the results suggest that CLIC1 modulates the metastasis of colon cancer through its RVD-mediating chloride channel function. This study demonstrates, for the first time, that CLIC1 regulates the migration and invasion of colon cancer.

Chloride Intracellular Channel 1 Regulates Prostate Cancer Cell Proliferation and Migration Through the MAPK/ERK Pathway

“…CLIC1 overexpression has been demonstrated in a wide variety of tumor types, including glioma 24 and colorectal cancer. 25 An elevated CLIC1 expression was strongly correlated with lymph node metastasis, perineural and lymphatic invasion, pathological staging, and poor survival. 26 However, the biological function and molecular mechanisms of CLIC1 in prostate cancer remain unclear.…”

Transmembrane voltage potential of somatic cells controls oncogene-mediated tumorigenesis at long-range

“…Roles for CLIC1 in carcinogenesis – albeit cell autonomous – have been shown previously in several studies. A search for ion channels in the cancer profiling database, Oncomine, turns up CLIC1 as one of the most upregulated genes [166], and chloride current associated with increased CLIC1 expression is present in progenitor cells isolated from human glioblastomas, and is responsible for promoting proliferation, clonogenicity, and tumorigenic capacity [167]. Channels like this are of high interest as a therapeutic modality [56], but it should be noted that it is not enough to look for blockers (a standard loss-of-function genetic strategy) – the key is to modulate V mem , which may mean opening or closing specific channels depending on the cells' surrounding milieu and its ion gradients.…”

Comparative proteomic analysis of two distinct stem-cell populations from human amniotic fluid

“…Interestingly, several studies describe a pivotal role of chloride intracellular channel protein in promoting cancer cell proliferation. [18][19][20] This protein is more expressed in fHASCs than in sHASCs and could contribute to the high proliferation rate observed in this line.…”