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G3BP1 通过与 YWHAZ 相互作用调节胃癌的化疗耐药性并预测辅助化疗获益。

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer.

机构信息

Department of General Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.

Cancer Center, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.

出版信息

Br J Cancer. 2021 Jan;124(2):425-436. doi: 10.1038/s41416-020-01067-1. Epub 2020 Sep 29.

DOI:10.1038/s41416-020-01067-1
PMID:32989225
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7852868/
Abstract

BACKGROUND

A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.

METHODS

Kaplan-Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.

RESULTS

G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1YWHAZ gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.

CONCLUSIONS

The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.

摘要

背景

很大一部分胃癌患者易发生化疗耐药，但其潜在机制尚不清楚。应激颗粒（SGs）在抑制化疗诱导的细胞凋亡方面为肿瘤细胞发挥自我保护作用。G3BP1（Ras-GTPase 激活蛋白 SH3 结构域结合蛋白）作为 SG 组装效应物，已被报道在胃癌中过表达；因此，我们旨在探索其在胃癌化疗耐药中的潜在作用。

方法

采用 Kaplan-Meier 分析比较不同 G3BP1 表达水平的胃癌患者的生存率。通过体外和体内方法评估 G3BP1 对胃癌细胞化疗耐药和凋亡的影响。通过免疫组织化学、免疫沉淀和免疫荧光评估 G3BP1 与 YWHAZ 之间的相互作用。

结果

G3BP1 与接受辅助化疗的胃癌患者的不良预后相关。G3BP1 敲低显著增加了胃癌细胞对化疗药物的敏感性。机制上，G3BP1 耗竭后细胞凋亡和促凋亡相关分子明显升高。基因共表达网络分析确定 YWHAZ 是 G3BP1 的关键中间层；结果，G3BP1 与 YWHAZ 相互作用将 Bax 隔离到细胞质中。临床上，与其他患者相比，G3BP1YWHAZ 胃癌患者在化疗后表现出最差的预后。

结论

G3BP1 和 YWHAZ 的表达可以预测胃癌患者辅助化疗的获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/4881af9095b6/41416_2020_1067_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/b14e7f91c3e7/41416_2020_1067_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/2fe1012b1b76/41416_2020_1067_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/1d2e2071fa32/41416_2020_1067_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/734feb561c99/41416_2020_1067_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/4881af9095b6/41416_2020_1067_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/b14e7f91c3e7/41416_2020_1067_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/2fe1012b1b76/41416_2020_1067_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/1d2e2071fa32/41416_2020_1067_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/734feb561c99/41416_2020_1067_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b30/7852868/4881af9095b6/41416_2020_1067_Fig5_HTML.jpg

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2
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Brief Bioinform. 2018 Jul 20;19(4):575-592. doi: 10.1093/bib/bbw139.
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4
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Front Mol Biosci. 2025 Jan 28;11:1521839. doi: 10.3389/fmolb.2024.1521839. eCollection 2024.
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