Tumor suppressor DAPK1 catalyzes adhesion assembly on rigid but anoikis on soft matrices

Abstract

Cancer cells will normally grow on soft surfaces, but if rigidity sensing modules are restored in cancer cells, they will undergo apoptosis on soft surfaces (anoikis) like most normal cells. DAPK1 is a major tumor suppressor that activates cell death, but it is unclear how DAPK1 could activate anoikis through rigidity sensing. Here we find that when rigidity sensing is decreased through inhibition of DAPK1 activity, cells are transformed for growth on soft matrices. Further, DAPK1 catalyzes matrix adhesion assembly and is part of adhesions on rigid surfaces. Additional factors include DAPK1 phosphorylation of tropomyosin2.1, talin1 head domain and tyrosine phosphorylation of DAPK1 by Src. On soft surfaces, DAPK1 rapidly dissociates from the adhesion complexes and activates apoptosis that requires PTPN12 activity and talin1 head. Thus, DAPK1 is important for adhesion assembly on rigid surfaces and the activation of anoikis on soft surfaces through its binding to rigidity-sensing modules.