TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer.

IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gastric Cancer Pub Date : 2024-09-01 Epub Date: 2024-06-08 DOI:10.1007/s10120-024-01517-2
Qiang Fu, Xuwei Wu, Zhongqi Lu, Ying Chang, Quanxin Jin, Tiefeng Jin, Meihua Zhang
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Abstract

Cisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP drug concentration in clinical treatment, cancer cells gradually became resistant. Therefore, it is necessary to find effective therapeutic targets to enhance the sensitivity of GC to DDP. Studies have shown that Transmembrane protein 205 (TMEM205) is overexpressed in DDP-resistant human epidermoid carcinoma cells and correlates with drug resistance, and database analyses show that TMEM 205 is also overexpressed in GC, but its role in cisplatin-resistant gastric cancer remains unclear. In this study, we chose a variety of experiments in vivo and vitro, aiming to investigate the role of TMEM 205 in cisplatin resistance in gastric cancer. The results showed that TMEM 205 promoted proliferation, stemness, epithelial-mesenchymal transition (EMT), migration and angiogenesis of gastric cancer cells through activation of the Wnt/β-catenin signaling pathway. In addition, TMEM205 promotes GC progression by inducing M2 polarization of tumor-associated macrophages (TAMs). These results suggest that TMEM205 may be an effective target to regulate the sensitivity of GC to DDP, providing a new therapeutic direction for clinical treatment.

Abstract Image

TMEM205诱导TAM/M2极化,促进胃癌的顺铂耐药性
顺铂(DDP)是胃癌(GC)的基本化疗药物。在临床治疗中,随着 DDP 药物浓度的增加,癌细胞逐渐产生耐药性。因此,有必要寻找有效的治疗靶点,以提高胃癌对 DDP 的敏感性。研究表明,跨膜蛋白205(TMEM205)在对DDP耐药的人表皮样癌细胞中过表达,并与耐药性相关,数据库分析表明,TMEM205在GC中也有过表达,但其在顺铂耐药胃癌中的作用仍不清楚。本研究选择了体内和体外的多种实验,旨在研究TMEM 205在胃癌顺铂耐药中的作用。结果表明,TMEM 205通过激活Wnt/β-catenin信号通路促进胃癌细胞的增殖、干性、上皮-间质转化(EMT)、迁移和血管生成。此外,TMEM205 还通过诱导肿瘤相关巨噬细胞(TAMs)的 M2 极化来促进胃癌的进展。这些结果表明,TMEM205可能是调节GC对DDP敏感性的有效靶点,为临床治疗提供了新的治疗方向。
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来源期刊
Gastric Cancer
Gastric Cancer 医学-胃肠肝病学
CiteScore
14.70
自引率
2.70%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.
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