Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability
Annual rept. 1 Sep 2012-31 Aug 2013
MICHIGAN UNIV ANN ARBOR
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It has been suggested that PHSCN inhibits metastatic invasion by forming a covalent, disulfide bond with a cysteine residue on the beta1 1 subunit of alpha5 beta1 5 1 integrin1. However, these studies were performed with purified 5 1 integrin, which also produces evidence of covalent bond formation with the 5 subunit tandem mass spectroscopy data not shown. Hence, the specificity of the reported interaction between PHSCN and the 1 subunit1 is suspect. Moreover, the cysteine rich 1 subunit can heterodimerize with 12 distinct alpha integrin subunits2, forming integrins that function in many pathways. In contrast, the 5 subunit interacts uniquely with the 1 subunit2 to induce invasion and support adhesion3-5 hence it is a much more desirable target.
- Medicine and Medical Research