Journal article

Laminin 521 enhances self-renewal via STAT3 activation and promotes tumor progression in colorectal cancer

Yan Qin, Carolyn Shembrey, Jai Smith, Sophie Paquet-Fifield, Corina Behrenbruch, Laura M Beyit, Benjamin NJ Thomson, Alexander G Heriot, Yuan Cao, Frederic Hollande

Cancer Letters | ELSEVIER IRELAND LTD | Published : 2020

Abstract

Remodeling of basement membrane proteins contributes to tumor progression towards the metastatic stage. One of these proteins, laminin 521 (LN521), sustains embryonic and induced pluripotent stem cell self-renewal, but its putative role in cancer is poorly described. In the present study we found that LN521 promotes colorectal cancer (CRC) cell self-renewal and invasion. siRNA-mediated knockdown of endogenously-produced laminin alpha 5, as well as treatment with neutralizing antibodies against integrin α3β1 and α6β1, were able to reverse the effect of LN521 on self-renewal. Exposure of CRC cells to LN521 enhanced STAT3 phosphorylation, and incubation with STAT3 inhibitors Napabucasin and Sta..

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Grants

Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia [grants number GNT1049561 and GNT1069024].