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Integrin expression and glycosylation patterns regulate cell-matrix adhesion and alter with breast cancer progression

Author:
Singh, Chandrajeet, Shyanti, Ritis K., Singh, Virendra, Kale, Raosaheb K., Mishra, Jai P.N., Singh, Rana P.
Source:
Biochemical and biophysical research communications 2018 v.499 no.2 pp. 374-380
ISSN:
0006-291X
Subject:
breast neoplasms, carcinogenesis, cell adhesion, cell lines, fibronectins, gene expression regulation, glycoproteins, glycosylation, integrins, messenger RNA, metastasis, neoplasm cells, swainsonine
Abstract:
Integrins are the major cell adhesion glycoproteins involved in cell-extracellular matrix (ECM) interaction and metastasis. Further, glycosylation on integrin is necessary for its proper folding and functionality. Herein, differential expression of integrins viz., αvβ3 and αvβ6 was examined in MDA-MB-231, MDA-MB-468 and MCF-10A cells, which signify three different stages of breast cancer development from highly metastatic to non-tumorigenic stage. The expression of αvβ3 and αvβ6 integrins at mRNA and protein levels was observed in all three cell lines and the results displayed a distinct pattern of expression. Highly metastatic cells showed enhanced expression of αvβ3 than moderate metastatic and non-tumorigenic cells. The scenario was reversed in case of αvβ6 integrin, which was strongly expressed in moderate metastatic and non-tumorigenic cells. N-glycosylation of αvβ3 and αvβ6 integrins is required for the attachment of cells to ECM proteins like fibronectin. The cell adhesion properties were found to be different in these cancer cells with respect to the type of integrins expressed. The results testify that αvβ3 integrin in highly metastatic cells, αvβ6 integrin in both moderate metastatic and non-tumorigenic cells play an important role in cell adhesion. The investigation typify that N-glycosylation on integrins is also necessary for cell-ECM interaction. Further, glycosylation inhibition by Swainsonine is found to be more detrimental to invasive property of moderate metastatic cells. Conclusively, types of integrins expressed as well as their N-glycosylation pattern alter during the course of breast cancer progression.
Agid:
5925404