Caveolin‐1 Mediates Inflammatory Breast Cancer Cell Invasion via the Akt1 Pathway and RhoC GTPase
Abstract
With a propensity to invade the dermal lymphatic vessels of the skin overlying the breast and readily metastasize, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. We previously reported that caveolin‐1 is overexpressed in IBC and that RhoC GTPase is a metastatic switch responsible for the invasive phenotype. RhoC‐driven invasion requires phosphorylation by Akt1. Using a reliable IBC cell line we set out to determine if caveolin‐1 expression affects RhoC‐mediated IBC invasion. Caveolin‐1 was down regulated by introduction of siRNA or a caveolin scaffolding domain. The ability of the cells to invade was tested and the status of Akt1 and RhoC GTPase examined. IBC cell invasion is significantly decreased when caveolin‐1 is down regulated. Activation of Akt1 is decreased when caveolin‐1 is down regulated, leading to decreased phosphorylation of RhoC GTPase. Thus, we report here that caveolin‐1 overexpression mediates IBC cell invasion through activation Akt1, which phosphorylates RhoC GTPase. J. Cell. Biochem. 116: 923–933, 2015. © 2015 Wiley Periodicals, Inc.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 10, 2015
- Source ID
- 10.1002/jcb.25025
Entities
People
- Heather L. Lehman
- Kenneth L. Van Golen
- Madhura Joglekar
- Matthew D. Weitzman
- Weam O. Elbazanti
Organizations
- Christiana Hospital
- Congressionally Directed Medical Research Programs
- University of Delaware