G protein pathway suppressor 2 suppresses gastric cancer by destabilizing epidermal growth factor receptor.
G protein pathway suppressor 2 suppresses gastric cancer by destabilizing epidermal growth factor receptor.
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G 蛋白通路抑制因子 2 通过破坏表皮生长因子受体的稳定性来抑制胃癌。
DOI：
10.1111/cas.15151
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发表时间：
2021-12
期刊：
影响因子：
5.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Si Y;Zhang H;Peng P;Zhu C;Shen J;Xiong Y;Liu X;Xiang Y;Li W;Ren Y;Wan F;Zhang L;Liu Y
G蛋白通路抑制因子2 （GPS2）在大多数人体组织中表达，包括胃。然而，GPS2在癌症中的生物学功能及其潜在的分子机制仍然知之甚少。在这里，我们报道GPS2在胃癌（GC）组织中的表达与对照组织相比异常下调。临床病理分析显示GPS2低表达与病理分级、淋巴结分期、浸润深度有显著相关性。Kaplan‐Meier分析显示，GPS2低表达患者的总生存率低于GPS2高表达患者。此外，GPS2过表达降低了胃癌细胞的增殖、集落形成、肿瘤发生和侵袭。GPS2过表达可降低GC细胞中表皮生长因子受体（EGFR）的蛋白表达，抑制其下游信号传导。有趣的是，GPS2降低了EGFR蛋白的表达，这被一种溶酶体抑制剂逆转。此外，GPS2通过增强EGFR与E3连接酶c‐Cbl的结合，降低了EGFR蛋白的稳定性，从而促进了EGFR的泛素化，最终导致其通过溶酶体途径降解。进一步分析表明，GPS2通过破坏EGFR的稳定，激活自噬，促进自噬通量。综上所述，这些结果表明GPS2低表达与胃癌进展有关，并为GPS2 - EGFR轴作为胃癌潜在治疗靶点的适用性提供了见解。G蛋白通路抑制因子2 （GPS2）在胃癌中低表达，低表达与预后不良相关。GPS2通过c - Cbl介导的泛素化和溶酶体降解降低表皮生长因子受体（EGFR）蛋白的稳定性。GPS2激活自噬，并通过破坏EGFR的稳定来促进自噬通量。
G protein pathway suppressor 2 (GPS2) is expressed in most human tissues, including the stomach. However, the biological functions of GPS2 in cancer, as well as the underlying molecular mechanisms, remain poorly understood. Here, we report that GPS2 expression was aberrantly downregulated in gastric cancer (GC) tissues compared with control tissues. Clinicopathologic analysis showed that low GPS2 expression was significantly correlated with pathological grade, lymph node stage, and invasive depth. Kaplan‐Meier analysis indicated that patients with low GPS2 expression showed poorer overall survival rates than those with high GPS2 expression. Moreover, GPS2 overexpression decreased GC cell proliferation, colony formation, tumorigenesis, and invasion. Overexpression of GPS2 reduced the protein expression of epidermal growth factor receptor (EGFR) and inhibited its downstream signaling in GC cells. Interestingly, GPS2 decreased EGFR protein expression, which was reversed by a lysosome inhibitor. Furthermore, GPS2 reduced EGFR protein stability by enhancing the binding of EGFR and an E3 ligase, c‐Cbl, which promoted the ubiquitination of EGFR, ultimately leading to its degradation through the lysosomal pathway. Further analysis indicated that GPS2 activated autophagy and promoted the autophagic flux by destabilizing EGFR. Taken together, these results suggest that low GPS2 expression is associated with GC progression and provide insights into the applicability of the GPS2‐EGFR axis as a potential therapeutic target in GC. G protein pathway suppressor 2 (GPS2) is expressed at low levels in gastric cancer and low GPS2 expression is associated with poor prognosis. GPS2 reduces epidermal growth factor receptor (EGFR) protein stability through c‐Cbl‐mediated ubiquitination and then lysosomal degradation. GPS2 activates autophagy and promotes the autophagic flux by destabilizing EGFR.
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影响因子：
8.8
作者：
Drareni K;Ballaire R;Barilla S;Mathew MJ;Toubal A;Fan R;Liang N;Chollet C;Huang Z;Kondili M;Foufelle F;Soprani A;Roussel R;Gautier JF;Alzaid F;Treuter E;Venteclef N
通讯作者：
Venteclef N
影响因子：
16
作者：
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Perissi, Valentina
影响因子：
5.5
作者：
Chan S;Smith E;Gao Y;Kwan J;Blum BC;Tilston-Lunel AM;Turcinovic I;Varelas X;Cardamone MD;Monti S;Emili A;Perissi V
通讯作者：
Perissi V
影响因子：
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作者：
Huang, Xiao-Dong;Xiao, Feng-Jun;Wang, Shao-Xia;Yin, Rong-Hua;Lu, Can-Rong;Li, Qing-Fang;Liu, Na;Zhang, Ying;Wang, Li-Sheng;Li, Pei-Yu
通讯作者：
Li, Pei-Yu
影响因子：
254.7
作者：
Jemal, A;Tiwari, RC;Thun, MJ
通讯作者：
Thun, MJ