LCN2 promotes focal adhesion formation and invasion by stimulating Src activation.

Choudhary, B. S.; Chaudhary, N. N.; Vijan, A. N.; Mandal, D.; Pilankar, L.; Gawand, S.; Khan, B. K.; Shivashankar, A.; Doloi, R.; Joshi, N.; Das, M.; Dalal, S. N.

doi:10.1101/2024.06.04.597324

bioRxiv · 10.1101/2024.06.04.597324

LCN2 promotes focal adhesion formation and invasion by stimulating Src activation.

Choudhary, B. S.·Chaudhary, N. N.·Vijan, A. N.·Mandal, D.·Pilankar, L.·Gawand, S.·Khan, B. K.·Shivashankar, A.·Doloi, R.·Joshi, N.·Das, M.·Dalal, S. N.

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Abstract

Previous work has demonstrated that Lipocalin2 (LCN2) expression promotes invasion and migration in multiple tumor types. The mechanisms by which LCN2 promotes invasion and migration remain unclear. Previous work from our laboratory demonstrated that LCN2 promotes actin filament formation by inhibiting actin glutathionylation. In this report, we demonstrate that in addition to inhibiting actin glutathionylation, LCN2 stimulates invasion by promoting the formation of focal adhesions, which is independent of the ability of LCN2 to bind iron. LCN2 promotes focal adhesion formation by promoting the activation of c-Src by stimulating the expression of the transcription factor ETS1. ETS1 activates the expression of the protein phosphatase, PTP1B, resulting in the auto-activation of c-Src and increased paxillin phosphorylation leading to focal adhesion formation. These results demonstrate that LCN2 has iron-dependent and independent functions in promoting invasion and highlight the multiple mechanisms by which LCN2 promotes invasion and suggest that c-Src inhibitors could be used to treat invasive colorectal cancer. SUMMARYExpression of LCN2 is elevated in invasive colorectal cancer. We demonstrate that LCN2 promotes invasion by stimulating the formation of focal adhesions by promoting Src activation.

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Choudhary, B. S., Chaudhary, N. N., Vijan, A. N., Mandal, D., Pilankar, L., Gawand, S., Khan, B. K., Shivashankar, A., Doloi, R., Joshi, N., Das, M., Dalal, S. N.. 2024-06-05. LCN2 promotes focal adhesion formation and invasion by stimulating Src activation.. https://doi.org/10.1101/2024.06.04.597324

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