LPP is a Src substrate required for invadopodia formation and efficient breast cancer lung metastasis

Elaine Ngan, Konstantin Stoletov, Harvey W. Smith, Jessica Common, William J. Muller, John D. Lewis and Peter M. Siegel ()
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Elaine Ngan: Goodman Cancer Research Centre, McGill University
Konstantin Stoletov: University of Alberta
Harvey W. Smith: Goodman Cancer Research Centre, McGill University
Jessica Common: Goodman Cancer Research Centre, McGill University
William J. Muller: Goodman Cancer Research Centre, McGill University
John D. Lewis: University of Alberta
Peter M. Siegel: Goodman Cancer Research Centre, McGill University

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract We have previously shown that lipoma preferred partner (LPP) mediates TGFβ-induced breast cancer cell migration and invasion. Herein, we demonstrate that diminished LPP expression reduces circulating tumour cell numbers, impairs cancer cell extravasation and diminishes lung metastasis. LPP localizes to invadopodia, along with Tks5/actin, at sites of matrix degradation and at the tips of extravasating breast cancer cells as revealed by intravital imaging of the chick chorioallantoic membrane (CAM). Invadopodia formation, breast cancer cell extravasation and metastasis require an intact LPP LIM domain and the ability of LPP to interact with α-actinin. Finally, we show that Src-mediated LPP phosphorylation at specific tyrosine residues (Y245/301/302) is critical for invadopodia formation, breast cancer cell invasion and metastasis. Together, these data define a previously unknown function for LPP in the formation of invadopodia and reveal a requirement for LPP in mediating the metastatic ability of breast cancer cells.

Date: 2017
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DOI: 10.1038/ncomms15059

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