(ALPHA) 2 (BETA) 1 Integrin-Induced Breast Cancer Differentiation
Abstract
Cell adhesive events play essential roles in the pathophysiology of breast cancer. Two important biological phenomena have been shown to depend upon integrins. The differentiation of breast cancer cells depends upon the expression of alpha2beta1 integrin on the cell surface. The creation of distant metastasis is supported by the association of breast cancer cells with platelets. This association depends on the interaction between the activated alpha2beta3 integrin on the breast cancer cell surface with the activated alphaIIbbeta3 integrin on the platelet surface. Thus, it is reasonable to assume that modulation of the function of those integrins may lead to the differentiation of poorly-differentiated breast cancer or the prevention of distant metastasis to other organs. To attain this goal, it is imperative to understand the precise mechanisms of integrin-ligand interaction. In this project I identified the ligand contact surfaces of alpha2beta1 and alphaIIbbeta3 integrins. The ligand contact site in alpha2beta1 is composed of several discontinuous amino acid residues surrounding the MIDAS in the alpha2beta1 domain. The alphaIIbbeta3 ligand binding interface is located on the outer edge and side of the propeller centering on beta-sheet 3 of the alphaIIb beta-propeller domain. These findings may form the basis for developing therapeutics for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA398563
Entities
People
- Tetsuji Kamata
Organizations
- Scripps Research