Localization of cortactin is associated with colorectal cancer development.
Cortactin is a ubiquitously expressed actin filament (F-actin)-binding protein that stabilizes F-actin networks and promotes actin polymerization by activating the actin-related protein 2/3 (Arp2/3) complex. Overexpression of cortactin in cancer cells stimulate cell migration, invasion, and experimental metastasis; however, the underlying mechanism in cortactin involvement in tumor progression is not fully understood. Recently, a direct interaction between zonula occludens-1 (ZO-1) and cortactin in epithelial cells was reported. The present study aimed to further clarify the significance of the interaction between cortactin and ZO-1 in cancer progression. Cortactin expression and localization in colorectal human cancer tissues were evaluated by immunohistochemistry and immunofluorescence. Co-immunoprecipitation and immunofluorescence analysis revealed cortactin and ZO-1 interaction and localization in cancer cells. In our study, the localization of cortactin is a crucial marker for lymph node metastasis in colorectal cancer. We show how the localization of cortactin effects cancer development. A molecular interaction between cortactin and ZO-1 in migrating or polarized cancer cells was revealed. This is the first report to show the interaction of cortactin and ZO-1 in colorectal cancer progression. We conclude that localization of cortactin in cancer cells and interaction between ZO-1 and cortactin are crucial for cancer progression.
Hirakawa
Hiroshi
H
Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. h-hira@nagasaki-u.ac.jp
Shibata
Kenichiro
K
Nakayama
Toshiyuki
T
D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism*; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
C495868:CTTN protein, human; D051356:Cortactin; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein