Collagen type I regulates beta-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells.
The interaction between tumor cells and the stroma environment has crucial effects on tumor cell invasive behavior. As a major component of the stroma, collagen plays a key role on cellular adhesion and epithelial-mesenchymal transition (EMT). Recently, we found that collagen type I is significantly up-regulated in gastric cancer tissues compared with their adjacent non-neoplastic tissues. However, whether collagen type I contributes to gastric cancer invasion and metastasis is not clear. Herein we show that, collagen type I induces cell scattering and cytoskeleton rearrangement, prompts cell migration and proliferation, which indicates that collagen type I is involved in promoting gastric cancer invasion and metastasis. Collagen type I is able to reduce cell-cell adhesion and enhance migration by inducing disassembly of the E-cadherin/catenin complex in gastric carcinoma cells, which is related to tyrosine phosphorylation of beta-catenin. Tyrosine phosphorylation of beta-catenin dissociates it from E-cadherin and actin cytoskeleton and facilitates its entry into the nucleus, where beta-catenin acts as a transcriptional activator inducing genes involved in cell proliferation. In conclusion, collagen type I contributes to invasion and metastasis by regulating beta-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells.
Li
Aiqing
A
Gastroenterology laboratory, Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, P.R. China.
Zhou
Tianhua
T
Guo
Lei
L
Si
Jianmin
J
D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D048430:Cell Shape; D024042:Collagen Type I / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014443:Tyrosine; D051176:beta Catenin / Q000378:metabolism*
D000199:Actins; D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D024042:Collagen Type I; D051176:beta Catenin; D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human