title: 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.
authors.affiliation: Department of Biological Sciences, The Center for Translational Cancer Research, The University of Delaware, Newark, Delaware; The Helen F. Graham Cancer Center, Newark, Delaware.
authors.forename: Madhura
authors.initials: M
authors.lastname: Joglekar
authors.forename: Weam O
authors.initials: WO
authors.lastname: Elbezanti
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
authors.forename: Heather L
authors.initials: HL
authors.lastname: Lehman
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: van Golen
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D020741:rho GTP-Binding Proteins
keywords: CAVEOLIN-1; INFLAMMATORY BREAST CANCER; INVASION; METASTASIS; RhoC GTPase