Genomics and Cancer Biology
Investigating Potential New Treatment Strategies for Late-Stage Breast Cancer
Rachel Hazan, PhD
Professor, Department of Pathology
Rachel Hazan, PhD, studies cadherin adhesion molecules and their role in metastatic breast cancer.
Aiming to expand the available options for treating late-stage breast cancer, the Hazan laboratory is investigating: 1) the molecular basis for cooperation between N-cadherin and the FGF receptor responsible for epithelial to mesenchymal transition (EMT) and metastasis with the goal of obtaining functional inhibitors of metastasis; 2) regulation of EMT and metastasis by the MAPK and AKT signaling pathways; 3) the relationship between cell cycle progression and tumor metastasis; 4) the mechanism of HER2 therapeutic resistance in breast cancer; and 5) cancer stem cells and their role in breast cancer metastasis.
Dr. Hazan and her team have shown that N-cadherin, a cadherin involved in dynamic processes such as cell migration and neurite outgrowth, is upregulated in invasive breast cancer cells and promotes metastasis of breast cancer cell lines. In contrast, E-cadherin, known to promote stable epithelial contacts, is lost during metastatic progression. Their data suggest that the shift in cadherin expression also affects proteolytic activity of cells, their migration, invasiveness and metastasis.
More recently, they discovered that Retinal cadherin (R-cadherin), a classic cadherin highly expressed in the brain and retina, is also present in the mammary epithelium. They showed that: 1) like E-cadherin, R-cadherin acts as an invasion-suppressor gene that is downregulated in invasive duct carcinomas; 2) R-cadherin knockdown in mammary-gland tissue leads to disruption of morphogenesis and gain of metastatic properties; 3) conversely, R-cadherin expression in aggressive tumor cells suppresses invasion and metastasis, and restores glandular morphogenesis.