GDF15通过保护性自噬增强胃癌的抗厌氧菌性和转移性

IF 4.4 2区 生物学 Q2 CELL BIOLOGY
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引用次数: 0

摘要

远处转移是导致胃癌(GC)患者死亡的一个普遍原因。细胞脱离细胞外基质(ECM)会导致细胞死亡,而细胞抗原(anoikis)是肿瘤转移的屏障。肿瘤细胞要想在循环系统中存活并转移,就必须获得抗anoikis能力。鉴别导致 GC 耐 anoikis 的分子过程至关重要,因为这可能有助于发现新的治疗靶点并改善 GC 患者的长期生存。在这项研究中,我们采用定量蛋白质组学方法确定了生长分化因子15(GDF15)是GC耐药的关键因素。我们发现,GDF15能增强保护性自噬,从而促进GC细胞的耐厌氧菌性。此外,通过DNA牵引试验,我们发现活化转录因子2(ATF2)是GDF15表达的关键调节因子,是GDF15的转录激活因子。这些发现共同表明,ATF2 和 GDF15 具有巨大的潜力,可作为候选靶点开发治疗策略,以解决 GC 的转移问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GDF15 enhances anoikis resistance and metastasis of gastric cancer through protective autophagy
Distant metastasis is a prevalent cause of mortality in gastric cancer (GC) patients. Anoikis, a process that induces cell death when cells get detached from the extracellular matrix (ECM), acts as a barrier to tumor metastasis. To survive in the circulatory system and metastasize, tumor cells must acquire anoikis resistance. It is crucial to identify the molecular processes that cause resistance to anoikis in GC since this might lead to the discovery of novel treatment targets and improve the long-term survival of GC patients. In this study, we employed quantitative proteomics to identify growth differentiation factor 15 (GDF15) as a key factor in GC anoikis resistance. We found that GDF15 enhances protective autophagy, thereby promoting anoikis resistance in GC cells. Furthermore, through DNA pull down assay, activating transcription factor 2 (ATF2) was found to be a critical regulator of GDF15 expression, acting as a transcriptional activator of GDF15. Collectively, these discoveries indicate that ATF2 and GDF15 have great potential as target candidates for developing therapeutic strategies to address the metastasis of GC.
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来源期刊
Cellular signalling
Cellular signalling 生物-细胞生物学
CiteScore
8.40
自引率
0.00%
发文量
250
审稿时长
27 days
期刊介绍: Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.
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