Spatial-temporal regulation of integrin activation, PI3K signaling, and podosome formation

Abstract

Extracellular signaling molecules can activate designated membrane receptors upon binding and trigger receptor oligomerization. Spatial-temporal clustering of membrane receptors serves as a reaction core for downstream biochemical reactions at the cellular interface. Integrin-mediated cell adhesion, a well-known example, involves micron-scale protein clustering and actin cytoskeleton remodeling at the interface of cell and extracellular matrices. I developed nano-patterned supported RGD membranes as a novel platform to decipher how mechanical cues in matrices regulate cell adhesion transformation. My recent report indicated that the formation of different adhesion structures, such as focal adhesion and podosome are modulated by mechanical characteristics of matrices. Lack of matrix-force at activated integrin clusters results in podosome formation in PI3K and FAK/PYK2 dependent manner. The switching between classic focal adhesions to macrophage-like podosomes is remarkable. While metastatic cancer cells also develop similar protrusive machinery, namely invadopodia, PI3K, FAK, and Pyk2 are all pharmaceutical targets to suppress tumor invasions. This groundbreaking finding directly suggests programmable adhesion transformation by matrix-mediated mechano-transduction.