G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer.
G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer.
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G3BP1 与 YWHAZ 相互作用调节化疗耐药性并预测胃癌辅助化疗的获益
DOI：
10.1038/s41416-020-01067-1
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发表时间：
2021-01
影响因子：
8.8
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Zhao J;Fu X;Chen H;Min L;Sun J;Yin J;Guo J;Li H;Tang Z;Ruan Y;Wang X;Sun Y;Huang L
大部分胃癌患者对化疗耐药敏感，但其潜在机制尚不清楚。应激颗粒（Stress Granules，SGs）在抑制化疗诱导的肿瘤细胞凋亡中起着自我防御的作用。G3BP1（Ras-GT3-activating protein SH3 domain-binding protein）作为一种SG组装效应子，在胃癌中有过表达，本研究旨在探讨G3BP1在胃癌化疗耐药中的作用。通过体外和体内实验研究G3BP1对胃癌细胞耐药和凋亡的影响。通过免疫组化、免疫沉淀和免疫荧光检测G3BP1与YWHAZ的相互作用，发现G3BP1与胃癌辅助化疗患者的不良预后相关，G3BP1敲除可显著增加胃癌细胞对化疗药物的敏感性。机械上，细胞凋亡和促凋亡相关分子在G3BP 1耗竭后显著升高。基因共表达网络分析表明YWHAZ是G3BP1的关键中间层，G3BP1与YWHAZ相互作用，将Bax螯合到细胞质中。结论G3BP1和YWHAZ的表达可预测胃癌患者辅助化疗的疗效。
BACKGROUNDA 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.METHODSKaplan–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.RESULTSG3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy.G3BP1knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated uponG3BP1depletion. 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, G3BP1highYWHAZhighgastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONSThe expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Nomura, M;Shimizu, S;Tsujimoto, Y
通讯作者：
Tsujimoto, Y
DOI：
10.6004/jnccn.2016.0137
发表时间：
2016-10-01
影响因子：
13.4
作者：
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通讯作者：
Sundar, Hema
影响因子：
158.5
作者：
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通讯作者：
Arai, Kuniyoshi
影响因子：
158.5
作者：
Cunningham, David;Allum, William H.;Chua, Yu Jo
通讯作者：
Chua, Yu Jo