Abstract 3084: Claudin-11 promotes cisplatin resistance by inducing autophagy through activation of the PHF23-ERK signaling pathway in ovarian cancer cells

Abstract Claudin-11, a member of claudins consisting of tight junction has been shown to be associated with prognosis and to play dual roles in cancer. However, its role in the response to anti-cancer agents is unknown. In this study, we investigated the role and mechanism of claudin-11 in cisplatin resistance in ovarian cancer. Kaplan-Meier survival analysis using The Cancer Genome Atlas data revealed that high CLDN11 expression is significantly associated with poor prognosis in ovarian cancer. Claudin-11 expression was significantly upregulated in cisplatin-resistant ovarian cancer cells. Consistent with this, claudin-11 overexpression significantly decreased the sensitivity to cisplatin in ovarian cancer cells. Cisplatin-induced apoptosis was reduced in claudin-11-overexpressing ovarian cancer cells, which was associated with decreased DNA damage. Moreover, claudin-11 overexpression inhibited cisplatin-induced apoptosis by promoting autophagy through increased ERK phosphorylation in ovarian cancer cells. The cisplatin sensitivity of claudin-11-overexpressing cells was restored by co-treatment with chloroquine, an autophagy inhibitor, and cisplatin, indicating that claudin-11 promotes cisplatin resistance by inducing autophagy. RNA sequencing data analysis further showed that autophagy-related PHD finger protein 23 (PHF23) is significantly upregulated in claudin-11-overexpressing cells compared with vector-transfected cells. PHF23 knockdown reversed cisplatin resistance by inhibiting ERK phosphorylation and then cisplatin-induced autophagy and apoptosis in claudin-11-overexpression cell. Taken together, these results indicate that claudin-11 promotes cisplatin resistance by activating autophagy through the PHF23-ERK signaling pathway and thereby reducing apoptosis in ovarian cancer cell, suggesting that inhibition of claudin-11 may overcome cisplatin resistance in ovarian cancer. Citation Format: Ha Yeong Chae, So Young Lee, Hyojin Jeong, Hye Ri You, Jinil Han, Young Kee Shin, Mi Jeong Kwon. Claudin-11 promotes cisplatin resistance by inducing autophagy through activation of the PHF23-ERK signaling pathway in ovarian cancer cells [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 3084.