Aberrant expression of claudin‐6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma

• DOI: 10.1111/cas.15284
• Publication Date: 2022-01-31T18:32:36Z
• Authors: Yui Ito; Akira Takasawa; Kumi Takasawa; Taro Murakami; Taishi Akimoto; Daisuke Kyuno; Yuka Kawata; Kodai Shano; Kurara Kirisawa; Misaki Ota; Tomoyuki Aoyama; Masaki Murata; Kotaro Sugimoto; Hideki Chiba; Tsuyoshi Saito; Makoto Osanai
• Keywords: Claudin

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark various solid tumors and it recognized as useful therapeutic target. Claudin-6 (CLDN6), member the family TJ transmembrane proteins, an ideal target because not expressed in human adult normal tissues. In this study, we found CLDN6 highly uterine cervical adenocarcinoma (ADC) high was correlated with lymph node metastasis lymphovascular infiltration independent prognostic factor. Shotgun proteome analysis cell-cell adhesion-related drug metabolism-associated (aldo-keto reductase [AKR] proteins) were significantly increased CLDN6-overexpressing cells. Furthermore, overexpression enhanced adhesion properties attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, cisplatin. Taken together, results indicate enhances malignant potentials resistance ADC, possibly due metabolism. Our findings provide insight into new strategy, CLDN6-targeting therapy, against ADC.