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EMT Blockage Strategies: Targeting Akt Dependent Mechanisms for Breast Cancer Metastatic Behaviour Modulation

[ Vol. 15 , Issue. 3 ]

Author(s):

D. Rafael, S. Doktorovova, H.F. Florindo, P. Gener, I. Abasolo, S.Jr. Schwartz and M.A. Videira   Pages 300 - 312 ( 13 )

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 wellknown 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.

Keywords:

Epithelial Mesenchymal Transition (EMT), E-cadherin, Metastization, , PI3K/AKT2/TWIST, RNAi nterference (RNAi)

Affiliation:

Faculty of Pharmacy, University of Lisbon, Intracellular Trafficking Modulation for Advanced Drug Delivery (InTraCell_ADD) research group, iMed.UL - Research Institute for Medicines and Pharmaceutical Sciences; Av. Prof. Gama Pinto 1649- 003, Lisbon-Portugal.



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