AUTHOR=Wang Jiahui , Kong Xianchao 

TITLE=IKBKE modulates autophagy and progestin resistance in endometrial cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1590966

DOI=10.3389/fonc.2025.1590966

ISSN=2234-943X

ABSTRACT=Background/objectivesEndometrial cancer (EC) is a prevalent malignancy in women, with up to 16% of cases diagnosed in individuals under 40 years old. Progestin-based therapies are essential for fertility preservation in EC patients, but resistance to these treatments remains a major challenge. IKBKE, an oncogenic kinase implicated in various cancers, including breast, ovarian, and prostate, has an unclear role in autophagy regulation and progestin resistance in EC. This study aims to investigate the involvement of IKBKE in these processes.MethodsA progestin-resistant EC cell line was established to assess the effects of IKBKE knockdown and treatment with CYT387, a selective IKBKE inhibitor. In vitro assays, including MTT viability, wound healing, colony formation, and Transwell invasion assays, were performed to evaluate cell proliferation, migration, and invasion. Autophagic activity was analyzed following CYT387 treatment.ResultsIKBKE knockdown significantly reduced cell proliferation, migration, in progestin-resistant EC cells. CYT387 treatment inhibited autophagic activity and decreased cell viability in these cells.ConclusionsThese findings highlight the crucial role of IKBKE in regulating autophagy and mediating progestin resistance in EC. This study provides new insights into IKBKE as a potential molecular target that contributes to understanding the mechanisms underlying progestin resistance in endometrial cancer.