Boudjadi Salah, Bernatchez Gérald, Sénicourt Blanche, Beauséjour Marco, Vachon Pierre H, Carrier Julie C, Beaulieu Jean-François
Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada.
Cancers (Basel). 2017 Jul 26;9(8):96. doi: 10.3390/cancers9080096.
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.
整合素是一类异源二聚体糖蛋白家族，参与双向细胞信号传导，在细胞形状、黏附、迁移、存活和增殖的调节中发挥作用。已知整合素α1β1参与RAS/ERK增殖途径的激活，并在成纤维细胞增殖中起重要作用。在小肠中，整合素α1亚基存在于隐窝增殖区，而在绒毛中不存在。我们最近发现，整合素α1蛋白和转录本（）在很大比例的结直肠癌（CRC）中存在，并且它们的表达受MYC致癌因子控制。鉴于在超过70%的结肠腺癌中α1亚基/的表达与MYC相关，我们推测整合素α1β1对CRC有促肿瘤作用。在HT29、T84和SW480 CRC细胞中，α1亚基/的敲低导致细胞增殖减少，同时HT29和T84细胞对失巢凋亡的抗性受损以及细胞迁移改变。此外，HT29和T84 sh-ITGA1细胞异种移植中的肿瘤发展减少，伴有广泛坏死、低有丝分裂指数和血管数量减少。我们的结果表明，α1β1参与肿瘤细胞的增殖、存活和迁移。这一发现表明α1β1促进CRC进展。
