Murata Toshihiro, Naomoto Yoshio, Yamatsuji Tomoki, Okawa Takaomi, Shirakawa Yasuhiro, Gunduz Mehmet, Nobuhisa Tetsuji, Takaoka Munenori, Sirmali Mehmet, Nakajima Motowo, Ohno Yuko, Tanaka Noriaki
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Int J Oncol. 2008 Apr;32(4):791-6.
Focal adhesion kinase (FAK) is an important mediator functioning between cells and the extracellular matrix and is closely related with the integrin-signaling pathway. FAK has been reported to be involved in the proliferation, differentiation and apoptosis of cells. To date, no report has demonstrated the involvement of FAK in the carcinogenesis of the digestive tract. Therefore, we examined colorectal, esophageal, pancreatic and mammary cancers for expression of FAK and Phospho (P)-FAK by immunohistochemistry. Strong expression of FAK in the cytoplasm was detected in all 4 tumor types and expressions of FAK and P-FAK increased as the degree of cell differentiation became higher in colorectal and esophageal carcinomas. Interestingly P-FAK expression was confined to the nuclei, which was an unexpected result. No previous report of such a finding has been published for gastrointestinal cancer. All four of the organs investigated in the present study showed P-FAK expression in the nuclei, suggesting an association between FAK activation and abnormal cell proliferation. We also performed immunostaining of P-FAK in cell lines to examine the significance of its experience in the nuclei. However, unlike clinical specimens, the cell lines did not show P-FAK expression in the nuclei. Moreover, the injection of cancer cells into the peritoneal cavity of mice also failed to demonstrate P-FAK expression in the nuclei. These results may be related with the function of carrier proteins of FAK such as Hic-5 and Zyxin, which are found only in humans. Taken together, FAK and P-FAK are involved in the carcinogenesis of digestive organs.
黏着斑激酶（FAK）是细胞与细胞外基质之间起作用的重要介质，与整合素信号通路密切相关。据报道，FAK参与细胞的增殖、分化和凋亡。迄今为止，尚无报道表明FAK参与消化道癌变过程。因此，我们通过免疫组织化学检测了结直肠癌、食管癌、胰腺癌和乳腺癌中FAK和磷酸化（P）-FAK的表达。在所有4种肿瘤类型中均检测到FAK在细胞质中的强表达，在结直肠癌和食管癌中，FAK和P-FAK的表达随着细胞分化程度的升高而增加。有趣的是，P-FAK的表达局限于细胞核，这是一个意外的结果。此前尚无关于胃肠道癌这一发现的报道。本研究中所调查的所有四个器官均显示细胞核中有P-FAK表达，提示FAK激活与细胞异常增殖之间存在关联。我们还对细胞系进行了P-FAK免疫染色，以研究其在细胞核中表达的意义。然而，与临床标本不同，细胞系未显示细胞核中有P-FAK表达。此外，将癌细胞注射到小鼠腹腔中也未能证明细胞核中有P-FAK表达。这些结果可能与FAK的载体蛋白如Hic-5和桩蛋白的功能有关，这些蛋白仅在人类中发现。综上所述，FAK和P-FAK参与消化器官的癌变过程。
