Interaction Between Cry61 and avbeta3 in Breast Cancer: Role in Texan Resistance
Abstract
The angiogenic factor Cyr61 (also known as CCN1) plays a key role in both the maintenance and the enhancement of a malignant phenotype in breast cancer. Cyr61 is overexpressed in about 30% of triple negative breast carcinomas, whereas Cyr61 expression levels in normal breast tissues are negligible. Our recent studies showed that Cyr61 overexpression renders human breast cancer cells highly resistance to the microtubule-interfering agent paclitaxel (Taxol), a current drug of choice for the treatment of metastatic breast cancer. We have confirmed that expression of alphavbeta3, a Cyr61 receptor, is markedly upregulated in breast cancer cells expressing alphavbeta3 Cyr61. Our most recent data demonstrate that functional blockade of with a synthetic chemical peptidomimetic based upon the the RGD (Arg-Gly-Asp) motif, is specifically cytotoxic towards Cyr61- overexpressing breast cancer. Pharmacological interference with the Cyr61/ interaction restores Taxol efficacy, implying that a previously unrecognized Cyr61/alphavbeta3 -driven cellular signaling actively modulates breast cancer cell growth, apoptosis and Chemosensitivity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA478662
Entities
People
- Ruth Lupu