title: The Interaction between Cancer Stem Cell Marker CD133 and Src Protein Promotes Focal Adhesion Kinase (FAK) Phosphorylation and Cell Migration.
abstract: CD133, a widely known cancer stem cell marker, has been proved to promote tumor metastasis. However, the mechanism by which CD133 regulates metastasis remains largely unknown. Here, we report that CD133 knockdown inhibits cancer cell migration, and CD133 overexpression promotes cell migration. CD133 expression is beneficial to activate the Src-focal adhesion kinase (FAK) signaling pathway. Further studies show that CD133 could interact with Src, and the region between amino acids 845 and 857 in the CD133 C-terminal domain is indispensable for its interaction with Src. The interaction activates Src to phosphorylate its substrate FAK and to promote cell migration. Likewise, a Src binding-deficient CD133 mutant loses the abilities to increase Src and FAK phosphorylation and to promote cell migration. Inhibition of Src activity by PP2, a known Src activity inhibitor, could block the activation of FAK phosphorylation and cell migration induced by CD133. In summary, our data suggest that activation of FAK by the interaction between CD133 and Src promotes cell migration, providing clues to understand the migratory mechanism of CD133(+) tumor cells.
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xing
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and.
authors.forename: Benjin
authors.initials: B
authors.lastname: Cao
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Division of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China ai.zhilong@zs-hospital.sh.cn.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Ai
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and yywei@fudan.edu.cn.
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: From the Key Laboratory of Glycoconjugates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, China and jianhaijiang@fudan.edu.cn.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; C000606023:PROM1 protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D054648:Protein Phosphatase 2
keywords: CD133; Src; focal adhesion kinase (FAK); migration; protein phosphorylation; protein-protein interaction; protein-tyrosine kinase 2 (PTK2)