Format

Send to

Choose Destination
J Biol Chem. 2016 Jul 22;291(30):15540-50. doi: 10.1074/jbc.M115.712976. Epub 2016 May 24.

The Interaction between Cancer Stem Cell Marker CD133 and Src Protein Promotes Focal Adhesion Kinase (FAK) Phosphorylation and Cell Migration.

Author information

1
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.
2
Division of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China ai.zhilong@zs-hospital.sh.cn.
3
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.
4
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.

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.

KEYWORDS:

CD133; Src; focal adhesion kinase (FAK); migration; protein phosphorylation; protein-protein interaction; protein-tyrosine kinase 2 (PTK2)

PMID:
27226554
PMCID:
PMC4957040
DOI:
10.1074/jbc.M115.712976
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center