biostudies-literatureUnknown21(12)Qu HProtective autophagy, a defensive response of cancer cells to chemotherapeutic stress, plays a critical role in the development of chemoresistance. Our previous research has demonstrated that the tight junction protein Claudin-6 (CLDN6) can induce autophagy and chemoresistance respectively. However, it remains unclear whether CLDN6 triggers protective autophagy under chemotherapeutic conditions. In this study, we focused on the role and mechanism of CLDN6 in inducing protective autophagy and promoting chemoresistance in breast cancer. We found that CLDN6 promoted chemoresistance by inducing protective autophagy in response to adriamycin (ADM) and paclitaxel (PTX). Mechanistically, CLDN6 interacted with LKB1 through its PDZ-binding motif, leading to the activation of AMPK/ULK1 signaling andInternational journal of biological sciences5444-5459https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435484biostudies-literatureCLDN6 induces chemoresistance through protective autophagy in breast cancer.PMC12435484Sun MQuan CJin QDong YQu HZhang MQi DfalseCLDN6 induces chemoresistance through protective autophagy in breast cancer.Protective autophagy, a defensive response of cancer cells to chemotherapeutic stress, plays a critical role in the development of chemoresistance. Our previous research has demonstrated that the tight junction protein Claudin-6 (CLDN6) can induce autophagy and chemoresistance respectively. However, it remains unclear whether CLDN6 triggers protective autophagy under chemotherapeutic conditions. In this study, we focused on the role and mechanism of CLDN6 in inducing protective autophagy and promoting chemoresistance in breast cancer. We found that CLDN6 promoted chemoresistance by inducing protective autophagy in response to adriamycin (ADM) and paclitaxel (PTX). Mechanistically, CLDN6 interacted with LKB1 through its PDZ-binding motif, leading to the activation of AMPK/ULK1 signaling and2025-01-01T00:00:00Z20252026-06-02T05:26:58.932Z2026-04-14T03:14:16.788ZS-EPMC124354844095928910.7150/ijbs.116340