Taking into account evidence of a PI3K-mediated activation of Rac1 in several tumor models (Haws et al., 2016; Ungefroren et al., 2018) and considering that Rac1 has been found to regulate TRPV2 intracellular trafficking in fibrosarcoma cells (Nagasawa and Kojima, 2015), it is possible to speculate that in PCa a PI3K-mediated Rac1 activation may allow the translocation to the plasma membrane of the “de novo” expressed TRPV2 in PC3 cells, thus giving rise of the TRPV2-mediated increase of cytosolic Ca2+ concentration responsible for MMPs overexpression. The gene discussed is RAC1; the disease is fibrosarcoma.