iTRAQ analysis of colorectal cancer cell lines suggests Drebrin (DBN1) is overexpressed during liver metastasis

Abstract

Colorectal cancer is currently the third in cancer incidence worldwide and the fourth most common cause of cancer deaths. Mortality in colorectal cancer is often ascribed to liver metastasis. In an effort to elucidate the proteins involved in colorectal cancer liver metastasis, we compared the proteome profiles of the human colon adenocarcinoma cell line HCT-116 with its metastatic derivative E1, using the iTRAQ labelling technology, coupled to 2D-LC and MALDI-TOF/TOF MS. A total of 547 proteins were identified, of which 31 of them were differentially expressed in the E1 cell line. Among these proteins, the differential expressions of translationally controlled tumour protein 1, A-kinase anchor protein 12 and Drebrin (DBN1) were validated using Western blot. In particular, DBN1, a protein not previously known to be involved in colorectal cancer metastasis, was found to be overexpressed in E1 as compared to HCT-116 cells. The overexpression of DBN1 was further validated using immunohistochemistry on colorectal cancer tissue sections with matched lymph node and liver metastasis tissues. DBN1 is currently believed to be involved in actin cytoskeleton reorganisation and suppresses actin filament cross-linking and bundling. Since actin reorganisation is an important process for tumour cell migration and invasion, DBN1 may have an important role during colorectal cancer metastasis.

Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer

“…In the present study, we found that CRIP1 is overexpressed in metastatic CRC tissues and in two highly metastatic colon cancer cell lines, SW620 and HT29. These results are consistent with a report that CRIP1 is overexpressed in the highly metastatic colon cancer cell line E1 compared with parental HCT-116 cells [13]. In addition, we found that CRIP1 expression was not associated with age, gender or tumour diameter, whereas increased CRIP1 was significantly associated withTNM stage, and lymphatic metastasis.…”

“…CRIP1 was found to be overexpressed in the highly metastatic colon cancer cell line E1, compared to the parental HCT-116 epithelial-like colon cells [13]. E1 cells display features characteristic of the epithelial–mesenchymal transition, and possess increased motility and invasiveness compared to parental HCT-116 cells.…”

Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis

“…MS-based cancer proteomic approaches have been widely used in recent years in search for potential CRC markers, using various biological specimen including cell lines, tissues and serum/plasma [11][12][13][14][15][16][17][18][19]. For example, Gan et al compared the proteome of well-differentiated and poorly-differentiated CRC tissues and adjacent normal epithelium to identify a number of novel proteins associated with CRC progression and differentiation [16].…”

Use of Gene Expression Analysis for Discrimination of Primary and Secondary Adenocarcinoma of the Liver

“…As for the other genes described above, until now there have been no reports on a potential function in human cholangiocarcinogenesis. In our study this gene was not expressed in colorectal metastasis, but there is one report on overexpression of this gene in a metastatic colon adenocarcinoma cell line [26]. Other reports describe this gene as a direct transcriptional target of the SOX11 transcription factor [27] and as a prognostic marker for lung cancer [28].…”