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Journal of Cell Communication and Signaling

, Volume 12, Issue 3, pp 513–527 | Cite as

Mechanistic regulation of epithelial-to-mesenchymal transition through RAS signaling pathway and therapeutic implications in human cancer

  • Kiran Tripathi
  • Minal Garg
Review

Abstract

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.

Keywords

Epithelial-to-mesenchymal transition (EMT) EMT-activating transcription factors MicroRNAs RAS activation and effector proteins RAS signaling 

Notes

Acknowledgements

One of the co-authors, KT is thankful to University Grants Commission (UGC), Govt. of India for providing research fellowship.

Compliance with ethical standards

Conflict-of-interests

Authors disclose no potential conflict-of interests.

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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of LucknowLucknowIndia

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