Novel inside-out regulation of laminin binding integrin function

picture of Joshua Gordon presenting his/her poster: Novel inside-out regulation of laminin binding integrin function

Joshua Gordon , Apollo Kascinta, Isis Sroka, Todd Anderson, Cynthia Sandoval and Anne E. Cress

Novel inside-out regulation of laminin binding integrin function

The dynamic regulation of tumor cell adhesion to laminin coated structures such as vessels and nerves is a major step in cancer metastasis. Tumors accomplish rapid deployment from laminin adhesion by enzymatic removal of the ligand binding domain of integrin A6B1 to yield a novel form called A6pB1. Although uPA/uPAR dependent proteolysis accomplishes the cleavage reaction, the cellular features that stimulate the cleavage event are unknown. The current study determined the influence of actin dynamics and the requirement for focal adhesion kinase activity or focal adhesion proteins paxillin or talin on teh production of A6pB1. Perturbation of actin filaments by cytochalasin D, latrunculin A and siRNA specific for actin, stimulates A6pB1 production. Similarly, blocking integrin dependent signaling (i.e., silencing focal adhesion kinase (FAK)) increased A6pB1 production. Interestingly, eliminating structural elements of focal adhesion sites (i.e. paxillin or talin) did not alter A6pB1 production. Taken together, these results suggest an "inside-out" type mechanism stimulates integrin cleavage through the uPA/uPAR axis.

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