Localization of FAK is related with colorectal carcinogenesis.
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.
Murata
Toshihiro
T
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Naomoto
Yoshio
Y
Yamatsuji
Tomoki
T
Okawa
Takaomi
T
Shirakawa
Yasuhiro
Y
Gunduz
Mehmet
M
Nobuhisa
Tetsuji
T
Takaoka
Munenori
M
Sirmali
Mehmet
M
Nakajima
Motowo
M
Ohno
Yuko
Y
Tanaka
Noriaki
N
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000209:etiology; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000209:etiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000209:etiology; D010534:Peritoneal Neoplasms / Q000201:enzymology / Q000209:etiology; D010766:Phosphorylation
D051416:Focal Adhesion Protein-Tyrosine Kinases