CircRNA调控ATG4B的液-液相分离,这是一种抑制癌症转移的新策略?

IF 4.1 Q2 CELL BIOLOGY
Cell Stress Pub Date : 2024-05-24 eCollection Date: 2024-01-01 DOI:10.15698/cst2024.05.296
Ziyuan Guo, Yang Chen, Yaran Wu, Jiqin Lian
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引用次数: 0

摘要

对于大多数脱落细胞来说,自噬是一种常见的程序性死亡,但癌细胞可以获得抗自噬能力,以促进其通过循环系统进行远处转移。研究表明,自噬通量的增强是许多癌细胞在脱落条件下存活的原因。靶向自噬过程的关键因子ATG4B可抑制体外癌症转移,但ATG4B缺陷小鼠易患多种严重疾病,这表明直接靶向ATG4B可能会产生不可控的副作用。在最近的研究中,我们证实 ATG4B 是胃癌细胞中一种新型的 RNA 结合蛋白。它与 circSPECC1 相互作用,从而促进了 ATG4B 的液-液相分离和泛素化。此外,m6A 阅读器 ELAVL1 可抑制 circSPECC1 的表达,从而提高 ATG4B 的表达和 GC 细胞的抗厌氧菌性。此外,我们还筛选出了一种美国 FDA 批准的化合物--洛匹那韦,它能恢复 circSPECC1 的丰度并抑制 GC 的转移。总之,我们的研究发现了一条新的信号通路(ELAVL1-circSPECC1-ATG4B-自噬)来促进GC细胞的耐药和转移,并筛选出了一种具有临床应用潜力的化合物来阻断这条通路,为预防GC转移提供了一种新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis?

Anoikis is a common programmed death for most of detached cells, but cancer cells can obtain anoikis resistance to facilitate their distant metastasis through the circulation system. Researches have indicated that enhanced autophagic flux accounts for the survival of many cancer cells under detached conditions. Targeting ATG4B, the key factor of autophagy progress, can inhibit cancer metastasis in vitro, but ATG4B-deficient mice are susceptible to many serious diseases, which indicates the potential uncontrolled side effects of direct targeting of ATG4B. In our recent research, we confirmed that ATG4B is a novel RNA binding protein in the gastric cancer (GC) cell. It interacts with circSPECC1 which consequently facilitates the liquid-liquid phase separation and ubiquitination of ATG4B. Additionally, the m6A reader ELAVL1 inhibits the expression of circSPECC1 to enhance the expression of ATG4B and anoikis resistance of GC cells. Further, we screened out an FDA-approved compound, lopinavir, to restore circSPECC1 abundance and suppress GC metastasis. In conclusion, our research identified a novel signal pathway (ELAVL1-circSPECC1-ATG4B-autophagy) to facilitate anoikis resistance and metastasis of GC cells and screened out a compound with clinical application potential to block this pathway, providing a novel strategy for the prevention of GC metastasis.

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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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