title: EMT blockage strategies: Targeting Akt dependent mechanisms for breast cancer metastatic behaviour modulation.
abstract: Epithelial Mesenchymal Transition (EMT) is an event where epithelial cells acquire mesenchymal-like phenotype. EMT can occur as a physiological phenomenon during tissue development and wound healing, but most importantly, EMT can confer highly invasive properties to epithelial carcinoma cells. The impairment of E-cadherin expression, an essential cell-cell adhesion protein, together with an increase in the expression of mesenchymal markers, such as N-cadherin, vimentin, and fibronectin, characterize the EMT process and are usually correlated with tumor migration, and metastization. A wide range of micro-environmental and intracellular factors regulate tumor development and progression. The dynamic cross-talk between the adhesion-related proteins such as E-cadherin and the EMT-related transcription factors, with special focus on TWIST, will be discussed here, with the aim of finding a suitable biological pathway to be used as potential target for cancer therapy. Emerging concepts such as the role of the PI3K/AKT/TWIST pathway in the regulation of the E-cadherin expression will be highlighted, since it seems to be consistently involved in cells EMT. The well-known efficacy of the RNA interference as a tool to silence the expression of specific proteins has come into focus as a strategy to control different tumor sub-populations. Despite the oligonucleotides enormous sensitivity and low in vivo stability, new (nano)technological solutions are expected to enable RNAi clinical application in cancer therapy.
authors.forename: D
authors.initials: D
authors.lastname: Rafael
authors.forename: S
authors.initials: S
authors.lastname: Doktorovová
authors.forename: H F
authors.initials: HF
authors.lastname: Florindo
authors.forename: P
authors.initials: P
authors.lastname: Gener
authors.forename: I
authors.initials: I
authors.lastname: Abasolo
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: M A
authors.initials: MA
authors.lastname: Videira
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D051057:Proto-Oncogene Proteins c-akt