Involvement of the Integrin α1β1 in the Progression of Colorectal Cancer

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 importa...

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Bibliographic Details
Published in:Cancers 2017-07, Vol.9 (8), p.96
Main Authors: Boudjadi, Salah, Bernatchez, Gérald, Sénicourt, Blanche, Beauséjour, Marco, Vachon, Pierre H, Carrier, Julie C, Beaulieu, Jean-François
Format: Article
Language:English
Subjects:
Anoikis
Blood vessels
Cell adhesion & migration
Cell growth
Cell migration
Cell proliferation
Cell size
Cell survival
Colorectal cancer
Colorectal carcinoma
Glycoproteins
Integrins
Kinases
Myc protein
Small intestine
Survival
Transcription
Villus
Xenografts
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Summary: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 ( ) 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/ 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/ 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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers9080096