Involvement of the Integrin α1β1 in the Progression of Colorectal Cancer

Abstract

Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling that participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin α1β1 is known to be involved in RAS/ERK proliferative pathway activation and plays an important role in fibroblast proliferation. In the small intestine, the integrin α1 subunit is present in the crypt proliferative compartment and absent in the villus. We have recently shown that the integrin α1 protein and transcript (ITGA1) are present in a large proportion of colorectal cancers (CRC) and that their expression is controlled by the MYC oncogenic factor. Considering that α1 subunit/ITGA1 expression is correlated with MYC in more than 70% of colon adenocarcinomas, we postulated that the integrin α1β1 has a pro-tumoral contribution to CRC. In HT29, T84 and SW480 CRC cells, α1 subunit/ITGA1 knockdown resulted in a reduction of cell proliferation associated with an impaired resistance to anoikis and an altered cell migration in HT29 and T84 cells. Moreover, tumor development in xenografts was reduced in HT29 and T84 sh-ITGA1 cells, associated with extensive necrosis, a low mitotic index and a reduced number of blood vessels. Our results show that α1β1 is involved in tumor cell proliferation, survival and migration. This finding suggests that α1β1 contributes to CRC progression.

TRMIntegrins CD103 and CD49a Differentially Support Adherence and Motility After Resolution of Influenza Virus Infection

“…While previous reports examining other cell types such as fibroblasts and endothelial cells suggested that CD49a's function was primarily to adhere to collagen, the differences observed could be attributed to distinct mechanisms mediating adhesion between cell types (38,41,42). Inhibition or knockdown of CD49a in tumor cells resulted in decreased migration compared with their CD49a sufficient counterparts (43,44). Similarly, human CD8 T cells ex vivo were unable to migrate through a collagen IV coated transwell when CD49a was blocked (45).…”

Integrin α6β4 in Colorectal Cancer: Expression, Regulation, Functional Alterations and Use as a Biomarker

“…It is interesting to note that the cells of the crypt proliferative compartment, which predominantly express α6A/ITGA6A [42,43], are also the cells that express MYC in the normal colon [9]. Experimental studies using a normal intestinal epithelial crypt cell line showed that MYC regulates ITGA6A expression [49].…”

“…This has been well documented recently for the α1β1 integrin, a collagen receptor. While exclusively expressed in the proliferative compartment in the normal colon, α1β1 was found to be overexpressed in CRC primary tumour and cell lines [7,8] and knockdown of α1 subunit expression resulted in the reduction of cell proliferation and tumour growth [9]. Integrin α9β1 is another interesting case.…”

Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer

“…To date, there are 18α and 8β subunits have been identified that can form 24 distinct protein receptors with binding to the corresponding ligands to mediate adhesion between cells and basal membrane of cells [9][10][11]. In this regard, integrins have gained great interest in studies of tumorigenesis, progression and metastasis, owing to their abilities to control the adhesion, migration, proliferation, invasion, and tumorigenicity of cancer cells [11,12]. Among them, the integrin α1 (ITGA1) is one of the important members of integrins [13], which was reported to significantly up-regulate in colorectal tumors and surrounding the tumour cells by immunohistochemical analysis [12,14].…”

“…In this regard, integrins have gained great interest in studies of tumorigenesis, progression and metastasis, owing to their abilities to control the adhesion, migration, proliferation, invasion, and tumorigenicity of cancer cells [11,12]. Among them, the integrin α1 (ITGA1) is one of the important members of integrins [13], which was reported to significantly up-regulate in colorectal tumors and surrounding the tumour cells by immunohistochemical analysis [12,14]. Boudjadi et al demonstrated that integrin α1β1 was positively correlated with CRC cell invasion and proliferation by activating the focal adhesion kinase (FAK)-src/p130Cas-JNK signaling cascades [6,12,14,15] and the Ras/MEK/ERK signaling pathway [16].…”