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