GP140/CDCPI in the Development of Prostate Cancer Metastasis
Abstract
We found that CDCP1 expression is decreased at the plasma membrane in invasive prostate cancers. This suggested that loss of CDCP1 may disrupt a normal epithelial cell function that contributes to a cancerous phenotype. In order to identify this hypotheltical normal cell function, required that we work with normal epithelial cells not immortal cell lines. This realization has caused a delay in work on Aim 3. We are pleased with our decision because it led to the identification of a novel signaling pathway GPCRs-SFK-CDCP1-PKCdelta and a novel cell function. Disruption of this pathway by knockdown of PKCdelta results in profound increases in SFK-mediated membrane protrusions. Membrane protrusions, in various forms including podosomes and invadopodia, are causal in invasion of cancer cells and remodeling of extracellular matrix. We are now determining if CDCP1 participates in this regulatory pathway through its interactions with PKCdelta and SFKs. We suggest that Gp140 restricts PKCdelta and SFK to the lateral and apical cell membrane and this suppresses membrane protrusions when GPCRs are activated. It is reasonable that the increased membrane protrusions may contribute to the loss of LM332 and hemidesmosomes in the basement membrane zone in prostate cancers. Our future research efforts will focus this new function for CDCP1 as a regulator of SFKs, PKCdelta and membrane protrusions.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2012
- Accession Number
- ADA562491
Entities
People
- William G. Carter
Organizations
- Fred Hutchinson Cancer Center