Abstract 5424: Exploring the potential role of PGC-1β in ovarian cancer malignancy

Mitochondrial metabolism plays a role in tumor development and metastasis. PGC-1β is recognized as a key regulator of mitochondrial biogenesis and metabolic activity. We have recently demonstrated that PGC-1β is a biomarker of addiction to mitochondrial metabolism in ovarian cancer and determines sensitivity to OXPHOS inhibitors. Its role in cancer is largely unexplored, but some reports suggest that PGC-1β exerts pro-tumorigenic actions. We aim at unraveling the influence of PGC-1β on ovarian cancer malignancy and how it regulates ovarian cancer cell functions, besides its metabolic role. To this purpose, murine ovarian cancer cells were silenced for PGC-1β and their behavior characterized in vitro and in vivo. First, we confirmed that PGC-1β silencing caused an alteration of oxidative metabolism by Seahorse analysis, showing the reduction of oxygen consumption. Then, we found that PGC-1β depletion did not affect ovarian cancer cell proliferation in standard culture conditions, but decreased proliferation compared to control cells in starvation conditions. Moreover, PGC-1β silenced cells showed reduced invasive potential, evidenced by decreased migration and invasion, associated to diminished collagenase activity. When injected in immunocompetent mice, PGC-1β silenced cells exhibited delayed tumor growth compared to control cells. In PGC-1β silenced tumor bearing mice ascites formation, a key indicator of disease progression, was reduced compared to controls, along with decreased metastatic dissemination in the peritoneal cavity. Our data suggest that the PGC-1β depletion reduces not only cancer cell ability to survive and proliferate under nutrient limited conditions, but also their invasive potential, leading to a delay in ovarian cancer progression in vivo. Further studies are needed to elucidate the underlying molecular pathways regulated by PGC-1β. (Supported by “HEAL ITALIA” project PE_00000019 to F.A., CUP: B43D22000710006) Citation Format: Laura Formenti, Francesca Abramo, Giulia Dellavedova, Raffaella Giavazzi, Carmen Ghilardi. Exploring the potential role of PGC-1β in ovarian cancer malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5424.