Collagen type I regulates β-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells
Collagen type I regulates β-catenin tyrosine phosphorylation and nuclear translocation to promote migration and proliferation of gastric carcinoma cells
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DOI：
10.3892/or_00000757
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发表时间：
2010-05-01
期刊：
影响因子：
4.2
通讯作者：
Si, Jianmin
中科院分区：
文献类型：
--
作者：
Li, Aiqing;Zhou, Tianhua;Si, Jianmin
肿瘤细胞与间质环境的相互作用对肿瘤细胞的侵袭行为有重要影响。胶原作为基质的主要成分，在细胞粘附和上皮-间质转化（EMT）中起着关键作用。近年来，我们发现I型胶原在胃癌组织中的表达明显高于癌旁组织。然而，I型胶原是否有助于胃癌的侵袭和转移尚不清楚。在此，我们发现，型胶原诱导细胞分散和细胞骨架重排，促进细胞迁移和增殖，这表明I型胶原参与促进胃癌的侵袭和转移。I型胶原通过诱导胃癌细胞中E-钙粘蛋白/连环蛋白复合物的分解而能够减少细胞-细胞粘附并增强迁移，这与β-连环蛋白的酪氨酸磷酸化有关。β-连环蛋白的酪氨酸磷酸化使其与E-钙粘蛋白和肌动蛋白细胞骨架分离，并促进其进入细胞核，其中β-连环蛋白作为转录激活剂诱导参与细胞增殖的基因。结论：I型胶原通过调节β-catenin酪氨酸磷酸化和核转位促进胃癌细胞的迁移和增殖，从而参与胃癌的侵袭和转移。
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 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.