Cytosolic Phospholipase A2 Determines Intercellular Heterogeneity of Stress Granules and Chemotherapy Response.

ABSTRACT: Cancer cell heterogeneity is a major therapeutic challenge. In this study, we identify that individual cells within cancer cell populations show significant heterogeneity in the levels of the stress-adaptive organelles, stress granules (SG), and demonstrate that SG heterogeneity is dictated by the cell cycle state. Specifically, SG formation is distinctively heightened in cells in the G2 phase because of the interplay between a nonapoptotic function of CASPASE-3 and calcium-dependent phospholipase A2 (cPLA2)-mediated production of the SG-promoting molecule, 15-deoxy-delta-prostaglandin-J2. We demonstrate that in the G1-S phase, CASPASE-3 cleaves and inactivates cPLA2, whereas in the G2 phase, CASPASE-3 activity is suppressed, resulting in enhanced cPLA2 activity and 15-deoxy-delta-prostagl

SUBMITTER: Redding A 

PROVIDER: S-EPMC12226220 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature