Role of RAC GTPase in Tumor Motility and Metastasis
Abstract
Metastasis of breast cancers contributes heavily to the severity and mortality of this disease. There is substantial evidence that integrins and small GTPases contribute to the metastatic properties of breast cancer cells enabling them to invade and migrate to distant sites throughout the body. This study provides evidence that Rac GTPase is required for both integrin and growth factor-mediated motility. Although Rac can activate JNK, not MAP kinase, we found it can interact with the Ras/MAP kinase pathway at the level of Raf kinase to regulate cell migration. One of the identified targets of Rac-GTP in cells are the p21-activated kinases (PAKs). PAKs can mediate many of the cytoskeletal changes induced by Rac and Cdc42. We show that cell adhesion can activate PAK through an integrin-dependent manner and PAK mediates cell spread and motility on extracellular matrix.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA379471
Entities
People
- Jie Leng
Organizations
- Scripps Research