A Molecular Approach for Metatastic Progression of Breast Cancer
Abstract
To elucidate the molecular mechanisms by which HER2/HRG influence migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src and FAK kinases. HER2, HRG system differentially regulate signaling from FAK by selectively dephosphorylating or activating some tyrosine residues and thus increase their migratory potential rather than adhesion. HRG promoted association of Tyr phosphatase PTPlD with HER2 and PTPlD has a role in HRG mediated dephopshorylation of FAK. HER2/HRG signaling selectively upregulated Tyr phosphorylation of c-Src at Tyr-2l5 located with in the SH2 domain, increased c-Src kinase activity and selectively upregulated Tyr phosphorylation of FAK at Tyr-86l. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215. Phosphospecific antibodies against the FAK and c-Src signaling molecules may potentially be used as an effective reagents to screen/identifying the putative metastatic/motile potential of breast tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA419679
Entities
People
- Ratna K Vadlamudi
Organizations
- University of Texas at Austin