The role of IFIT3 for the pro-inflammatory microenvironment of pancreatic cancer pathogenesis

IFIT3在胰腺癌发病机制促炎微环境中的作用

• 批准号: 316568276
• 负责人: Professorin Dr. Christiane Josephine Bruns
• 金额: --
• 依托单位: Klinik und Poliklinik für Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316568276?language=en
• 关键词: role; IFIT3; pro; inflammatory; microenvironment

Ductal pancreatic adenocarcinoma (PDAC) belongs to the most common tumor-associated causes of death. Up to now, prognosis and survival of PDAC stay unfavorable. Recent research reports demonstrate a correlation between pancreatitis and the development of PDAC. Our preliminary results clearly show that IFIT3 (Interferon-Induced Protein With Tetratricopeptide Repeats 3) is a pro-carcinogenic protein for PDAC which is upregulated upon treatment with interferon-alpha. The aim of this proposal is to investigate whether IFIT3 acts as an interface between inflammation and PDAC carcinogenesis and partly responsible for the failure of interferon-alpha treatment of PDAC. Important aspects of this hypothesis have to be experimentally proven as follows:a) the role of IFIT3 as anti-apoptotic protein being neutralized via binding of the pro-apoptotic protein IFIT2,b) the participation of IFIT3 at the Sox9-IFIT3-STAT3-AP1 signal transduction cascade via its function as a scaffold protein, andc) the capability of IFIT3 to activate the production of pro-inflammatory cytokines leading to the phenomenon of local pseudoinflammation and establishment of a tumor growth supporting milieu.The results could contribute to a better understanding of the relationship between pancreatic carcinogenesis, pancreatitis, IFN-alpha-signal transduction and IFIT3 as pro-carcinogenic scaffold-protein

胰腺导管腺癌（PDAC）属于最常见的肿瘤相关死亡原因。迄今为止，PDAC的预后和生存率仍然很差。最近的研究报告表明胰腺炎和PDAC的发展之间存在相关性。我们的初步结果清楚地表明，IFIT 3（干扰素诱导的蛋白与Tetratricopeptide Repeats 3）是PDAC的促癌蛋白，其在用干扰素-α治疗后上调。该建议的目的是研究IFIT 3是否作为炎症和PDAC致癌作用之间的界面，并部分负责PDAC的干扰素-α治疗失败。这一假设的重要方面必须通过实验证明如下：a）IFIT 3作为抗凋亡蛋白的作用通过结合促凋亡蛋白IFIT 2而被中和，B）IFIT 3通过其作为支架蛋白的功能参与Sox 9-IFIT 3-STAT 3-AP 1信号转导级联，以及c）IFIT 3激活促炎细胞因子的产生从而导致局部假炎症现象和建立肿瘤生长支持环境的能力。IFN-α信号转导和IFIT 3作为促癌支架蛋白

项目成果

The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer

IL-17A/IL-17RA 轴与胰腺癌的总体存活率和癌症干细胞调节无关

• DOI: 10.3390/ijms21062215
• 发表时间: 2020
• 期刊: International Journal of Molecular Sciences
• 影响因子: 5.6
• 作者: Betzler C;Lohneis P;Popp MC;Kalinski T;Wartmann T;Bruns CJ;Zhao Y;Popp FC
• 通讯作者: Popp FC

Tumor-Derived Extracellular Vesicles Inhibit Natural Killer Cell Function in Pancreatic Cancer

• DOI: 10.3390/cancers11060874
• 发表时间: 2019-06
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Jiangang Zhao;H. Schlößer;Zhefang Wang;J. Qin;Jiahui Li;F. Popp;M. Popp;H. Alakus;S. Chon;H. Hansen;W. Neiss;K. Jauch;C. Bruns;Yue Zhao

Inflammatory IFIT3 renders chemotherapy resistance by regulating post-translational modification of VDAC2 in pancreatic cancer

• DOI: 10.7150/thno.43093
• 发表时间: 2020-01-01
• 期刊: THERANOSTICS
• 影响因子: 12.4
• 作者: Wang, Zhefang;Qin, Jie;Bruns, Christiane J.
• 通讯作者: Bruns, Christiane J.

Interferon-Induced Protein With Multiple Tetratricopeptide Repeats 3 Is Associated With Response to Chemotherapy and Recurrence but Not With Survival.

具有多个四三肽重复序列 3 的干扰素诱导蛋白与化疗反应和复发相关，但与生存无关

• DOI: 10.1097/mpa.0000000000001691
• 发表时间: 2020
• 期刊: Pancreas
• 影响因子: 2.9
• 作者: Popp MC;Klippstein M;Lohneis P;Kalinski T;Quaas A;Bludau M;Wang Z;Waldschmidt D;Kunzmann V;Damanakis A;Gebauer F;Zhao Y;Bruns CJ;Popp FC
• 通讯作者: Popp FC

Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma

干扰素诱导蛋白四三肽重复序列 3 (IFIT3) 升高是胰腺导管腺癌的不良预后标志物

• DOI: 10.1007/s00432-017-2351-4
• 发表时间: 2017
• 期刊: Journal of Cancer Research and Clinical Oncology
• 影响因子: 3.6
• 作者: Yue Zhao;Annelore Altendorf-Hofmann;Ioannis Pozios;Peter Camaj;Therese Däberitz;Xiaoyan Wang;Hanno Niess;Hendrik Seeliger;Felix Popp;Christopher Betzler;Utz Settmacher;Karl-Walter Jauch;Christiane Bruns;Thomas Knösel
• 通讯作者: Thomas Knösel