RAS-mediated oncogenic signaling pathways in human malignancies

Semin Cancer Biol. 2019 Feb:54:1-13. doi: 10.1016/j.semcancer.2018.03.001. Epub 2018 Mar 7.

Abstract

Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and associated pathological conditions including cancer. In general, RAS is the main upstream regulator of the highly conserved signaling mechanisms associated with a plethora of important cellular activities vital for normal homeostasis. Mutated or the oncogenic RAS aberrantly activates a web of interconnected signaling pathways including RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase), phosphoinositide-3 kinase (PI3K)/AKT (protein kinase B), protein kinase C (PKC) and ral guanine nucleotide dissociation stimulator (RALGDS), etc., leading to uncontrolled transcriptional expression and reprogramming in the functioning of a range of nuclear and cytosolic effectors critically associated with the hallmarks of carcinogenesis. This review highlights the recent literature on how oncogenic RAS negatively use its signaling web in deregulating the expression and functioning of various effector molecules in the pathogenesis of human malignancies.

Keywords: Malignancies; Mutation; Oncogenes; RAS proteins; Signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Humans
  • Immunomodulation / genetics
  • Inflammation / genetics
  • Inflammation / metabolism
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Oncogenes
  • S-Phase Kinase-Associated Proteins / genetics
  • S-Phase Kinase-Associated Proteins / metabolism
  • Signal Transduction*
  • Structure-Activity Relationship
  • Transcription Factors / metabolism
  • ras Proteins / chemistry
  • ras Proteins / genetics*
  • ras Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • S-Phase Kinase-Associated Proteins
  • Transcription Factors
  • ras Proteins