{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T02:59:33Z","timestamp":1786762773430,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      We and others have shown that elevated human Group IIA secreted phospholipase A\n                      <jats:sub>2<\/jats:sub>\n                      (hGIIA) has both catalysis-dependent and -independent functions that are associated with both acute and chronic inflammatory disorders including cancer. Our novel inhibitors that selectively block hGIIA\u2019s catalysis-independent function slow tumor growth in animal models via interaction with vimentin. The mechanism of this interaction and its consequences for cancer aggressiveness remains unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We have used established patient-derived androgen-independent prostate cancer (PCa) cell lines, DU145, PC-3 and vimentin-knockout DU145 (DU145\n                      <jats:sup>vim\u2212<\/jats:sup>\n                      ) cells treated with hGIIA protein in the presence and absence of our cyclic peptide inhibitor Kesonotide (also known as c2). As lipid metabolism is known to be regulated by vimentin, we examined whether this aspect of vimentin biology was influenced by interaction with hGIIA, focusing on lipid droplet (LD) formation, LD-associated perilipin proteins (PLIN2 and PLIN3) and lipid biosynthetic enzymes (DGAT and FASN). To do this we used the combination of single cell quantitative immunofluorescence and Western blot analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that addition of exogenous hGIIA increased LD metabolism as evidenced by LD immunofluorescence signal and this increase is dependent on vimentin in PCa. The response is dependent on hGIIA levels with high concentrations of hGIIA associated with PLIN2 loss, PLIN3 suppression, and DGAT1 induction without FASN upregulation. Kesonotide alone was largely inert. However, at high concentration of hGIIA, Kesonotide attenuated lipid metabolism by neutralizing perilipin remodelling and attenuating DGAT1 induction in knockout cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Taken together, these findings identify a context-dependent hGIIA LD-remodelling program that is shaped by vimentin, implicating for the first time the hGIIA\u2013vimentin axis in inflammatory cue\u2013driven lipid metabolic rewiring in aggressive PCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1774027","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:39:55Z","timestamp":1779082795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The innate immune mediator group IIA secreted phospholipase A2 modulates lipid droplet 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