AKAP2 coordinates a focal adhesion signaling scaffold to promote growth and metastasis in triple-negative breast cancer
A Kinase Anchoring Proteins (AKAPs) that coordinate spatiotemporal signaling are increasingly implicated in cancer. Elevated AKAP2 protein correlates with an invasive phenotype in triple-negative breast cancer cell lines. A combination of biochemical, cellular, and omics approaches show that AKAP2 cytoskeleton and focal adhesion associated scaffolds contribute to the progression of basal-like triple-negative breast cancer. Proximity proteomics identifies AKAP2 as an element of focal adhesions in MDA-MB-231 cells. Molecular and immunofluorescent microscopy studies demonstrate that AKAP2 indirectly constrains focal adhesion kinase (FAK). Gene silencing of AKAP2 not only decreases FAK levels but also attenuates the phosphorylation of the cell motility adapter protein paxillin on Tyr118. Cell-derived xenograft studies in mice establish that AKAP2 is required for triple-negative breast cancer growth and metastasis, phenotypes that are linked to FAK action. These findings discover a new role for focal adhesion-associated AKAP2 in triple-negative breast cancer pathology. Overall design: RNAseq profiling of shScramble MDA-MB-231 cells and shAKAP2 MDA-MB-231 cells in the presence or absence of doxycycline. Doxycycline induces the expression of the shRNA promoter.