Gastrin/CCK-B Receptor Signaling Promotes Cell Invasion and Metastasis by Upregulating MMP-2 and VEGF Expression in Gastric Cancer.
Gastrin/CCK-B Receptor Signaling Promotes Cell Invasion and Metastasis by Upregulating MMP-2 and VEGF Expression in Gastric Cancer.
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胃泌素/CCK-B 受体信号通过上调胃癌中 MMP-2 和 VEGF 表达促进细胞侵袭和转移
DOI：
10.7150/jca.51854
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发表时间：
2022
影响因子：
3.9
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Zhao Y;Wang Q;Zeng Y;Xie Y;Zhou J
越来越多的证据表明，胃泌素和胆囊收缩素B受体（CCK-BR）组成的功能环可能存在于胃癌发生过程中。然而，由于缺乏直接证据，这一建议并不完全得到支持，其潜在机制也不完全清楚。在这里，我们评估了胃泌素/CCK-BR信号传导对细胞生长、侵袭、MMP-2和VEGF表达以及体内异种移植物生长的影响。此外，我们检测了人胃癌组织、转移淋巴结和邻近非肿瘤组织中胃泌素mRNA的含量。我们发现强制胃泌素可以通过上调MMP-2和VEGF的表达促进胃癌细胞的增殖、迁移和侵袭。使用Proglumide （CCK-BR拮抗剂）或shRNA阻断gastrin的胃泌素/CCK-BR信号可显著抑制促胃泌素的作用。体内研究表明，接种胃泌素过表达细胞的裸鼠肿瘤生长明显快于对照细胞。胃癌患者转移淋巴结中胃泌素mRNA的含量高于原发性胃癌和癌旁非肿瘤组织。总之，我们提供了胃泌素/CCK-BR信号在胃癌发生和发展中的直接证据和可能的机制。
Accumulated evidence suggests that a functional loop composed of gastrin and cholecystokinin B receptor (CCK-BR) may exist in gastric carcinogenesis. However, this suggestion is not completely supported due to a lack of direct evidence, and the underlying mechanism is not completely understood. Here, we evaluated the effects of gastrin/CCK-BR signaling on the cell growth, invasion, and expression of MMP-2 and VEGF, as well as xenograft growth in vivo. Furthermore, we detected gastrin mRNA content in human gastric cancer tissues, metastatic lymph nodes, and adjacent nontumor tissues. We found that the forced gastrin could promote the proliferation, migration, and invasion of gastric cancer cells by upregulating the expression of MMP-2 and VEGF. Blocking gastrin/CCK-BR signal using either Proglumide, a CCK-BR antagonist, or shRNA against GASTRIN significantly inhibited the gastrin-promoting effects. In vivo study revealed that the tumor growth in nude mice inoculated with gastrin-overexpressed cells was significantly faster than control cells. The gastrin mRNA content in metastatic lymph nodes was higher in patients with gastric cancer than in primary gastric cancer and adjacent nontumor tissues. In conclusion, we provided direct evidence and possible mechanism of gastrin/CCK-BR signaling in the initiation and progression of gastric cancer.
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影响因子：
9.2
作者：
Smith JP;Fonkoua LK;Moody TW
通讯作者：
Moody TW
在肿瘤胃细胞中胆囊化蛋白-B受体的表达。
影响因子：
3
作者：
Mjønes P;Nordrum IS;Sørdal Ø;Sagatun L;Fossmark R;Sandvik A;Waldum HL
通讯作者：
Waldum HL
影响因子：
2.5
作者：
Macedo F;Ladeira K;Longatto-Filho A;Martins SF
通讯作者：
Martins SF
胃蛋白会激活自噬并增加胃腺癌细胞的迁移和存活。
影响因子：
3.8
作者：
Rao SV;Solum G;Niederdorfer B;Nørsett KG;Bjørkøy G;Thommesen L
通讯作者：
Thommesen L
影响因子：
29.4
作者：
Tomita H;Takaishi S;Menheniott TR;Yang X;Shibata W;Jin G;Betz KS;Kawakami K;Minamoto T;Tomasetto C;Rio MC;Lerkowit N;Varro A;Giraud AS;Wang TC
通讯作者：
Wang TC