Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells.
Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells.
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胃蛋白会激活自噬并增加胃腺癌细胞的迁移和存活。
DOI：
10.1186/s12885-017-3055-5
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发表时间：
2017-01-21
期刊：
影响因子：
3.8
通讯作者：
Thommesen L
中科院分区：
文献类型：
--
作者：
Rao SV;Solum G;Niederdorfer B;Nørsett KG;Bjørkøy G;Thommesen L
肽激素胃泌素在正常和恶性胃肠道组织中都发挥促生长作用。胃泌素通过胆囊收缩素2受体（CCKBR/CCK 2 R）介导其作用。虽然相当一部分胃腺癌表达胃泌素和CCK BR，但胃泌素在肿瘤发展中的作用尚不完全清楚。自噬与细胞保护、肿瘤生长的机制有关，并导致化疗耐药性。本研究探讨了自噬在胃腺癌细胞系中对胃泌素反应的作用。免疫印迹、存活测定和xCELLigence系统用于研究胃泌素诱导的自噬。利用自噬的化学抑制剂来评估该过程在调节由胃泌素诱导的细胞反应中的作用。此外，使用siRNA和免疫印迹进行敲低研究以探索响应于胃泌素处理而激活自噬的信号传导途径。我们证明胃泌素增加胃腺癌细胞中自噬标志物MAP 1 LC 3B-II和SQSTM 1的表达。胃泌素通过激活STK 11-PRKAA 2-ULK 1诱导自噬，并且该信号传导途径参与增加的迁移和细胞存活。此外，胃泌素介导的顺铂处理的细胞存活率的增加部分依赖于诱导的自噬。这项研究揭示了胃泌素在自噬调节中的新作用。它还通过靶向CCKBR介导的信号传导和/或自噬与常规细胞抑制药物组合，开辟了治疗胃癌的新途径。本文的在线版本（doi：10.1186/s12885-017-3055-5）包含补充材料，可供授权用户使用。
The peptide hormone gastrin exerts a growth-promoting effect in both normal and malignant gastrointestinal tissue. Gastrin mediates its effect via the cholecystokinin 2 receptor (CCKBR/CCK2R). Although a substantial part of the gastric adenocarcinomas express gastrin and CCKBR, the role of gastrin in tumor development is not completely understood. Autophagy has been implicated in mechanisms governing cytoprotection, tumor growth, and contributes to chemoresistance. This study explores the role of autophagy in response to gastrin in gastric adenocarcinoma cell lines. Immunoblotting, survival assays and the xCELLigence system were used to study gastrin induced autophagy. Chemical inhibitors of autophagy were utilized to assess the role of this process in the regulation of cellular responses induced by gastrin. Further, knockdown studies using siRNA and immunoblotting were performed to explore the signaling pathways that activate autophagy in response to gastrin treatment. We demonstrate that gastrin increases the expression of the autophagy markers MAP1LC3B-II and SQSTM1 in gastric adenocarcinoma cells. Gastrin induces autophagy via activation of the STK11-PRKAA2-ULK1 and that this signaling pathway is involved in increased migration and cell survival. Furthermore, gastrin mediated increase in survival of cells treated with cisplatin is partially dependent on induced autophagy. This study reveals a novel role of gastrin in the regulation of autophagy. It also opens up new avenues in the treatment of gastric cancer by targeting CCKBR mediated signaling and/or autophagy in combination with conventional cytostatic drugs. The online version of this article (doi:10.1186/s12885-017-3055-5) contains supplementary material, which is available to authorized users.
胃蛋白受体拮抗剂的治疗作用，CR2093对胃肠道肿瘤细胞生长。
影响因子：
8.8
作者：
Watson, S A;Crosbee, D M;Morris, D L;Robertson, J F;Makovec, F;Rovati, L C;Hardcastle, J D
通讯作者：
Hardcastle, J D