https://scholars.lib.ntu.edu.tw/handle/123456789/456361
標題: | Cyr61 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by Raf-1/MEK/ERK/Elk-1/TWIST-1 signaling pathway | 作者: | CHUN-HAN HOU Lin F.-L. Hou S.-M. Liu J.-F. |
公開日期: | 2014 | 出版社: | BioMed Central Ltd. | 卷: | 13 | 期: | 1 | 來源出版物: | Molecular Cancer | 摘要: | Background: Osteosarcoma is the most common primary malignant tumor in children and young adults, and its treatment requires effective therapeutic approaches because of a high mortality rate for lung metastasis. Epithelial to mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining the invasive and metastatic behavior during cancer progression. The cysteine-rich angiogenic inducer 61 (Cyr61) gene, a member of the CCN gene family, is responsible for the secretion of Cyr1, a matrix-associated protein that is involved in several cellular functions. A previous study showed that Cyr61 expression is related to osteosarcoma progression. In addition, Cyr61 could promote cell migration and metastasis in osteosarcoma. However, discussions on the molecular mechanism involved in Cyr61-regulated metastasis in osteosarcoma is poorly discussed. Results: We determined that the expression level of Cyr61 induced cell migration ability in osteosarcoma cells. The Cyr61 protein promoted the mesenchymal transition of osteosarcoma cells by upregulating mesenchymal markers (TWIST-1 and N-cadherin) and inhibiting the epithelial marker (E-cadherin). Moreover, the Cyr61-induced cell migration was mediated by EMT. The Cyr61 protein elicited a signaling cascade that included αvβ5 integrin, Raf-1, mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and Elk-1. The reagent or gene knockdown of these signaling proteins could inhibit Cyr61-promoted EMT in osteosarcoma. Finally, the knockdown of Cyr61 expression obviously inhibited cell migration and repressed mesenchymal phenotypes, reducing lung metastasis. Conclusion: Our results indicate that Cyr61 promotes the EMT of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves αvβ5 integrin, Raf-1, MEK, ERK, and Elk-1. ? 2014 Hou et al.; licensee BioMed Central Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84934911486&doi=10.1186%2f1476-4598-13-236&partnerID=40&md5=583a9ea7f5faf74647487845897c145c https://scholars.lib.ntu.edu.tw/handle/123456789/456361 |
ISSN: | 1476-4598 | DOI: | 10.1186/1476-4598-13-236 | SDG/關鍵字: | alphaVbeta5 integrin; cysteine rich protein 61; mitogen activated protein kinase; mitogen activated protein kinase kinase; nerve cell adhesion molecule; protein TWIST 1; Raf protein; transcription factor Elk 1; transcription factor Twist; unclassified drug; uvomorulin; alphaVbeta5 integrin; cysteine rich protein 61; mitogen activated protein kinase; mitogen activated protein kinase kinase; Raf protein; transcription factor Elk 1; transcription factor Twist; tumor marker; vitronectin receptor; animal experiment; animal model; animal tissue; Article; cell migration; controlled study; epithelial mesenchymal transition; gene silencing; human; human cell; lung metastasis; male; metastasis; mouse; nonhuman; osteosarcoma; protein expression; signal transduction; upregulation; animal; cell motion; disease model; enzymology; gene expression regulation; genetics; metabolism; metastasis; osteosarcoma; pathology; phenotype; tumor cell line; Animals; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cysteine-Rich Protein 61; Disease Models, Animal; Epithelial-Mesenchymal Transition; ets-Domain Protein Elk-1; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Mice; Mitogen-Activated Protein Kinase Kinases; Neoplasm Metastasis; Osteosarcoma; Phenotype; raf Kinases; Receptors, Vitronectin; Signal Transduction; Twist Transcription Factor |
顯示於: | 醫學系 |
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