title: Collagen type I regulates beta-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells.
abstract: 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.
authors.affiliation: Gastroenterology laboratory, Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, P.R. China.
authors.forename: Aiqing
authors.initials: A
authors.lastname: Li
authors.forename: Tianhua
authors.initials: T
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Jianmin
authors.initials: J
authors.lastname: Si
mesh_terms: 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*
chemical_list: 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