Yu Hong-Gang, Tong Shi-Lun, Ding You-Ming, Ding Jian, Fang Xiang-Min, Zhang Xian-Feng, Liu Zhu-Jun, Zhou Yan-Hong, Liu Qi-Sheng, Luo He-Sheng, Yu Jie-Ping
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China.
Int J Cancer. 2006 Dec 15;119(12):2724-32. doi: 10.1002/ijc.22207.
Focal adhesion kinase (FAK) is suggested to be intimately involved in the progression of malignancies. Our previous research has demonstrated that activation of cholecystokinin-2 receptor (CCK2R) by gastrin stimulates a rapid activation of FAK pathway in human colon cancer cells. The purpose of this study is to determine the role of CCK2R and FAK in the progression of colon cancer. In this study, matched tissue samples of primary colon cancer and adjacent normal colon mucosa from the same patient were collected from 45 patients with colon cancer undergoing surgical resection. The gastrin expression was detected using reverse transcription polymerase chain reaction (RT-PCR). The CCK2R expression was examined by in situ hybridization and RT-PCR. The expression of FAK and phosphorylated FAK at tyrosine 397 (phospho-FAK) were detected using immunohistochemistry and immunoblotting. Colo320 and SW787, 2 colon cancer cell lines with or without CCK2R expression, were recruited in this study. Antisense oligonucleotide of FAK was used to block the expression of FAK. Invasiveness and motility of colon cancer cells were detected by Boyden chamber. In this series, enhanced expression of gastrin, CCK2R, FAK and phospho-FAK were observed in colon cancer tissues. CCK2R expression correlated with expression of phospho-FAK. Coexpression of CCK2R and phospho-FAK associated with invasion and lymph node metastasis. Increased invasion and motility was induced by gastrin in Colo320 cells. Overexpression of CCK2R by stable transfection of CCK2R plasmid amplified this increase and incubation with 1 microM L-365,260, a specific CCK2R antagonist, completely inhibited the effect of gastrin. FAK antisense largely blocked the increase of invasion and motility in Colo320 cells. Our data represent the evidence for the CCK2R regulating invasion and motility of colon cancer cells, and support a role of CCK2R in the progression of colon cancer. FAK play a critical role in this CCK2R-mediated effect.
粘着斑激酶（FAK）被认为与恶性肿瘤的进展密切相关。我们之前的研究表明，胃泌素激活胆囊收缩素-2受体（CCK2R）可刺激人结肠癌细胞中FAK通路的快速激活。本研究的目的是确定CCK2R和FAK在结肠癌进展中的作用。在本研究中，从45例接受手术切除的结肠癌患者中收集了同一患者的原发性结肠癌和相邻正常结肠黏膜的配对组织样本。使用逆转录聚合酶链反应（RT-PCR）检测胃泌素表达。通过原位杂交和RT-PCR检测CCK2R表达。使用免疫组织化学和免疫印迹检测FAK和酪氨酸397位点磷酸化FAK（磷酸化FAK）的表达。本研究纳入了Colo320和SW787这2种有或无CCK2R表达的结肠癌细胞系。使用FAK反义寡核苷酸阻断FAK的表达。通过Boyden小室检测结肠癌细胞的侵袭性和运动性。在这一系列研究中，在结肠癌组织中观察到胃泌素、CCK2R、FAK和磷酸化FAK的表达增强。CCK2R表达与磷酸化FAK的表达相关。CCK2R和磷酸化FAK的共表达与侵袭和淋巴结转移相关。胃泌素诱导Colo320细胞的侵袭和运动性增加。通过稳定转染CCK2R质粒使CCK2R过表达放大了这种增加，并且与1μM L-365,260（一种特异性CCK2R拮抗剂）孵育可完全抑制胃泌素的作用。FAK反义寡核苷酸在很大程度上阻断了Colo320细胞侵袭和运动性的增加。我们的数据为CCK2R调节结肠癌细胞的侵袭和运动性提供了证据，并支持CCK2R在结肠癌进展中的作用。FAK在这种CCK2R介导的效应中起关键作用。
Zotero 插件