GBP2 enhances paclitaxel sensitivity in triple-negative breast cancer by promoting autophagy in combination with ATG2 and inhibiting the PI3K/AKT/mTOR pathway

作者全名："Zhang, Weidan; Tang, Xin; Peng, Yang; Xu, Yingkun; Liu, Li; Liu, Shengchun"

作者地址："[Zhang, Weidan; Peng, Yang; Xu, Yingkun; Liu, Li; Liu, Shengchun] Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Zhang, Weidan] Peoples Hosp Tongliang, Dept Gen Surg, Chongqing 402560, Peoples R China; [Tang, Xin] Peoples Hosp Tongliang, Dept Rehabil Med, Chongqing 402560, Peoples R China"

通信作者："Liu, SC (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001175312300001

JCR分区：Q1

影响因子：5.2

年份：2024

卷号：64

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：guanylate-binding protein 2; triple-negative breast cancer; autophagy; paclitaxel; therapeutic target

摘要："Chemoresistance is a major challenge in treating triple-negative breast cancer (TNBC); chemotherapy remains the primary approach. The present study aimed to elucidate the role of guanylate-binding protein 2 (GBP2) in activating autophagy in TNBC and its impact on the sensitivity of TNBC cells to paclitaxel (PTX). Transfection with lentivirus was performed to establish TNBC cell lines with stable, high GBP2 expression. The mRNA and protein levels of GBP2 expression were evaluated utilizing reverse transcription-quantitative PCR and western blotting, respectively. Autophagy in TNBC cells was evaluated using immunoblotting, transmission electron microscopy and fluorescence microscopy. The PI3K/AKT/mTOR pathway proteins and their phosphorylation were detected by immunoblotting, and fluorescence co-localization analysis was performed to evaluate the association between GBP2 and autophagy-related protein 2 (ATG2). BALB/c NUDE mice were subcutaneously injected with GBP2 wild-type/overexpressing MDA-MB-231 cells. Low GBP2 expression was detected in TNBC, which was associated with a poor prognosis. Overexpression of GBP2 suppressed cell growth, and especially enhanced autophagy in TNBC. Forced expression of GBP2 significantly increased the PTX sensitivity of TNBC cells, and the addition of autophagy inhibitors reversed this effect. GBP2 serves as a prognostic marker and exerts a notable inhibitory impact on TNBC. It functions as a critical regulator of activated autophagy by co-acting with ATG2 and inhibiting the PI3K/AKT/mTOR pathway, which contributes to increasing sensitivity of TNBC cells to PTX. Therefore, GBP2 is a promising therapeutic target for enhancing TNBC treatment."

基金机构：Key Research and Development Project of Chongqing's Technology Innovation and Application Development Special Big Health Field

基金资助正文：Not applicable.