Fig. 7: A working model of Kindlin-2-AR-Src signaling in breast cancer cells.

The picture depicts a model in which the Kindlin-2-AR-Src complex delineated in the current study promotes AR Tyr-534 phosphorylation, downstream signaling, breast cancer cell proliferation and migration. A In wild-type breast cancer cells, Kindlin-2 acts as a scaffold to recruit Src and AR to form a supramolecular complex, and thereby facilitates Src-dependent AR Tyr-534 phosphorylation and promotes AR nuclear translocation in response to EGF stimulation, leading to increased expression of AR target genes, breast cancer cell proliferation and migration. B In Kindlin-2 deficient cells, loss of Kindlin-2 impairs the complex formation between Src and AR, resulting in diminished AR Tyr-534 phosphorylation, signaling, breast cancer cell proliferation and migration. In Kindlin-2 deficient cells expressing AR-binding-defective mutant (Kindlin-2-ΔF1) (C) or Src-binding-defective mutant (Kindlin-2-ΔF0) (D), the Kindlin-2 mutants are unable to promote the formation of a supramolecular complex containing both Src and AR, and therefore are unable to promote Src-dependent AR Tyr-534 phosphorylation, signaling, breast cancer cell proliferation and migration. E, F In Kindlin-2 deficient cells expressing phospho-mimic mutant of AR (AR Y534D) promotes AR nuclear translocation, and then increases AR target genes expression, breast cancer cell proliferation and migration (E). However, overexpression of wild-type AR (AR WT) in Kindlin-2 knockdown cells failed to do so (F).