Up-regulated PSMA expression in aggressive prostate tumors implies a selective advantage for expressing cells and therefore a role for PSMA in cancer cell growth and progression. Previous and herein shown results demonstrate that PSMA clustering at LNCaP surface activates beta1 integrin, AKT/mTOR/BAD pathway and p38 and ERK1/2 MAPKs, thus promoting cell growth and apoptosis resistance. This occurs thanks to the assembly of complexes including Filamin A, beta1 integrin, phospho p130CAS and phospho Src1. Immunoblottings, FACS analysis and 3D cultures demonstrated that PSMA-induced kinase activation and rescue were hampered or abrogated if Filamin A or beta1 integrin were silenced, or if Src1 was inhibited with SU6656 or PP1 drugs. In addition, beta1 integrin activation was halved in Src-inhibited cells or in Filamin A-silenced LNCaP. These results highlight the existence of a PSMA/beta1 integrin cooperation in the LNCaP growth and survival and the Filamin A ability to extend beta1 integrin partnership to molecules other than growth factor or cytokine receptors.
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