Abstract 6721: NUAK2: The key player in ovarian cancer progression - Unraveling the impact of expression and nuclear localization

Abstract Background: NUAK2 is a kinase related to the catalytic α-subunits of the AMP-activated protein kinase (AMPK) complexes. Although NUAK2 is amplified in several human cancers, its role in cancer is poorly understood. By immunohistochemical study, we demonstrated that elevated nuclear expressed NUAK2 is associated with poor ovarian cancer patient survival and more aggressive cancer cell behaviour. Exploring the implications of NUAK2 in ovarian cancer could offer valuable perspectives on disease development and patient prognosis. Aim: To delineate the impact of NUAK2 nuclear localization on cellular mechanisms crucial for tumor proliferation, and metastasis. Methods: Lentiviral expression vectors harbouring wild type NUAK2 (NUAK2-WT) and NUAK2 NLS mutant (NUAK2-375AAAA378) were used to transduce KF and OVCA420, two ovarian cancer cell lines expressing low level of endogenous NUAK2. Cytoplasmic localization of NUAK2-375AAAA378 was confirmed by immunoblotting and immunofluorescence microscopy. The impact on cell growth was evaluated by CCK8 assay and colony formation assay. The ability of the transduced cells in migration and invasion was compared with wound healing assay and transwell assay. Results: Mutating the NLS excluded NUAK2 from the nucleus. Cells expressing NUAK2-375AAAA378 proliferated significantly slower and migrated significantly slower than cells expressing NUAK2-WT. Conclusion: The study's outcomes indicated nuclear localization is crucial for NUAK2’s oncogenic functions in enhancing the proliferation and migration capabilities of ovarian cancer cells. These results underscore the crucial role of NUAK2 in ovarian cancer progression. Citation Format: Cong Xu, O.G.W Wong, Annie.N.Y Cheung. NUAK2: The key player in ovarian cancer progression - Unraveling the impact of expression and nuclear localization [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 6721.