Open AccessMechanistic regulation of epithelial‐to‐mesenchymal transition through RAS signaling pathway and therapeutic implications in human cancer
Author(s) -
Tripathi Kiran,
Garg Minal
Publication year - 2018
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-017-0441-3
Subject(s) - reprogramming , epithelial–mesenchymal transition , microrna , epigenetics , signal transduction , gene silencing , effector , cancer research , cancer , mapk/erk pathway , biology , bioinformatics , metastasis , cell , microbiology and biotechnology , gene , genetics
RAS effector signaling instead of being simple, unidirectional and linear cascade, is actually recognized as highly complex and dynamic signaling network. RAF‐MEK‐ERK cascade, being at the center of complex signaling network, links to multiple scaffold proteins through feed forward and feedback mechanisms and dynamically regulate tumor initiation and progression. Three isoforms of Ras harbor mutations in a cell and tissue specific manner. Besides mutations, their epigenetic silencing also attributes them to exhibit oncogenic activities. Recent evidences support the functions of RAS oncoproteins in the acquisition of tumor cells with Epithelial‐to‐mesenchymal transition (EMT) features/ epithelial plasticity, enhanced metastatic potential and poor patient survival. Google Scholar electronic databases and PubMed were searched for original papers and reviews available till date to collect information on stimulation of EMT core inducers in a Ras driven cancer and their regulation in metastatic spread. Improved understanding of the mechanistic basis of regulatory interactions of microRNAs (miRs) and EMT by reprogramming the expression of targets in Ras activated cancer, may help in designing effective anticancer therapies. Apparent lack of adverse events associated with the delivery of miRs and tissue response make ‘drug target miRNA’ an ideal therapeutic tool to achieve progression free clinical response.