Date of Award
Master of Science
Dr. Moshmi Bhattacharya
The small GTPase Rapl regulates cell adhesion, cell survival, gene transcription and invasion. We have found that Rapl activity can be stimulated by the bioactive lipid lysophosphatidic acid (LPA) in human breast cancer cells, but not in non-malignant mammary epithelial cells. The G protein-coupled LPA] receptor has been implicated in breast cancer metastasis although the molecular mechanisms underlying this process are largely unknown. We show that Rapl expression is higher in breast cancer cell lines and tissue. Gene knockdown of Rapl expression significantly impaired LPA-stimulated migration and invasion of breast cancer cells. We found that Rapl interacts with the multi-functional scaffolding proteins P-arrestin2 and IQGAP1 that are critical regulators breast cancer cell invasiveness. Additionally, P-arrestin2 and IQGAP1 associate in response to LPA and IQGAP1 knockdown blocks breast cancer invasion. Thus, our data suggests a novel mechanism by which LPA regulates breast cancer cell invasiveness via Rapl, P-arrestin2, and IQGAP1.
Alemayehu, Mistre, "P-ARRESTIN REGULATES LYSOPHOSPHATIDIC ACID-INDUCED HUMAN BREAST CANCER CELL INVASIVENESS VIA RAP1 AND IQGAP1" (2010). Digitized Theses. 3720.