Proteomic Analysis of Epithelial to Mesenchymal Transition (EMT) Reveals Cross-talk between SNAIL and HDAC1 Proteins in Breast Cancer Cells

• DOI: 10.1074/mcp.m115.052910
• Publication Date: 2016-01-14T04:20:49Z
• Authors: Camila de Souza P...; Mariana Lopes Grassi; Carolina Hassibe ...; Germano Aguiar Fe...; Daniele Albuquerque; Mariana Tomazini ...; Fernanda Ursoli F...; Simone Kashima; Dimas Tadeu Covas; Sharon J. Pitteri; Vitor M. Faça
• Keywords: HDAC1

Epithelial to mesenchymal transition (EMT)(1) occurs naturally during embryogenesis, tissue repair, cancer progression, and metastasis. EMT induces cellular microenvironmental changes resulting in loss of epithelial acquisition phenotypes, which promotes invasive migratory capabilities. can be triggered by extracellular factors, including TGF-β, HGF, EGF. Overexpression transcription such as SNAIL, SLUG, ZEB1/2, TWIST1, also is correlated aggressiveness. Here, the breast adenocarcinoma cell line MCF7 was transduced with SNAIL identify specific mechanisms controlled this factor EMT. led EMT, thoroughly validated molecular, morphological, functional experiments. Subcellular proteome enrichment followed GEL-LC-MS/MS performed provide extensive protein fractionation in-depth proteomic analysis. Quantitative analysis relied on a SILAC strategy, using MDA-MB-231 reference for quantitation. Subsets proteins enriched each subcellular compartment complementary list 4289 identified high confidence. A subset differentially expressed Western blot, regulation compartments, potentially caused translocation. Protein network highlighted complexes involved cycle control epigenetic regulation. Flow cytometry indicated that overexpression arrest G0/G1 phases. Furthermore, down-regulation HDAC1 observed, supporting involvement processes SNAIL-induced When activity inhibited, not only apparently initiated but up-regulated indicating cross-talk between these two proteins. Both inhibition activated AKT pathway. These molecular appear essential therefore Specific might then represent effective approaches clinical management metastatic cancer.