Altered Cdc42 Signaling in Metastatic Breast Cancer Cells
Abstract
The ability of cells to change their shape and move is critical to many biological processes. Cancer metastasis, the process whereby cancer cells leave a primary tumor and proliferate at distant sites, is highly dependent on cell shape changes and cell motility. The Rho GTPases play major roles in regulating the organization of the actin cytoskeleton and cell motility. Cdc42, one of the Rho GTPases, exerts its biological effects through interaction with downstream effector proteins. We identified a new family of Cdc42 effector proteins called SPECs for Small Protein Effector of Cdc42. The two human members of this family, SPEC1 and SPEC2 contain a centrally located CRIB domain through which they bind Cdc42. Overexpression of SPEC1 and SPEC2 in NIH-3T3 fibroblasts resulted in the formation of plasma membrane blebbing and modified Cdc42-induced biological activities when co-expressed with Cdc42. JNK kinase assays revealed that SPEC1 inhibited Cdc42-induced JNK activation. Northern blot analysis showed that SPEC1 is alternatively spliced and exists in at least four different molecular weight species. Additional Northern blot data using RNA from a panel of breast cancer cell lines suggests that SPEC1 expression may decrease in more metastatically aggressive breast cancer cell lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA404766
Entities
People
- Dana M. Pirone
Organizations
- Georgetown University