BAG3-IFITM2 轴通过 MAPK 信号通路促进胰腺导管腺癌生长

IF 3.3 3区 医学 Q2 ONCOLOGY
Peipei Wang, Congliang Chen, Kexin Lin, Yu Zhang, Junmei Hu, Tongbo Zhu, Xia Wang
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引用次数: 0

摘要

胰腺导管腺癌(PDAC)是一种致死率极高的恶性肿瘤,其发病率和死亡率不断攀升,因此迫切需要找到新的治疗靶点和策略。BAG3 蛋白是一种参与多种细胞过程的多功能调控因子,在促进肿瘤进展方面起着至关重要的作用,是肿瘤与肿瘤微环境之间的潜在 "桥梁"。本研究表明,PDAC 细胞分泌的 BAG3(sBAG3)可与 IFITM2 受体结合,激活 MAPK 信号通路,特别是增强 pERK 活性,从而促进 PDAC 的生长。此外,我们初步研究了 sBAG3 对共培养 NK 细胞的影响,发现 sBAG3 会降低 NK 细胞的细胞毒性和活性分子的表达。总之,我们的研究结果证实了 sBAG3-IFITM2 轴在促进 PDAC 进展中的关键作用,突出了 sBAG3 作为肿瘤和免疫细胞双重治疗靶点的潜在意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The BAG3-IFITM2 Axis Enhances Pancreatic Ductal Adenocarcinoma Growth via the MAPK Signaling Pathway.

Pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, exhibits escalating incidence and mortality rates, underscoring the urgent need for the identification of novel therapeutic targets and strategies. The BAG3 protein, a multifunctional regulator involved in various cellular processes, notably plays a crucial role in promoting tumor progression and acts as a potential "bridge" between tumors and the tumor microenvironment. In this study, we demonstrate that PDAC cells secrete BAG3 (sBAG3), which engages the IFITM2 receptor to activate the MAPK signaling pathway, specifically enhancing pERK activity, thereby propelling PDAC growth. Furthermore, our preliminary investigation into the effects of sBAG3 on co-cultured NK cells intriguingly discovered that sBAG3 diminishes NK cell cytotoxicity and active molecule expression. In conclusion, our findings confirm the pivotal role of the sBAG3-IFITM2 axis in fostering PDAC progression, highlighting the potential significance of sBAG3 as a dual therapeutic target for both tumor and immune cells.

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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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