RAS-mediated oncogenic signaling pathways in human malignancies

Abdul Q. Khan, Shilpa Kuttikrishnan, Kodappully S. Siveen, Kirti S. Prabhu, Muralitharan Shanmugakonar, Hamda A. Al-Naemi, Mohammad Haris, Said Dermime, Shahab Uddin

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23 Citations (Scopus)

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.

Original languageEnglish
JournalSeminars in Cancer Biology
DOIs
Publication statusAccepted/In press - 1 Jan 2018

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Keywords

  • Malignancies
  • Mutation
  • Oncogenes
  • RAS proteins
  • Signaling

ASJC Scopus subject areas

  • Cancer Research

Cite this

Khan, A. Q., Kuttikrishnan, S., Siveen, K. S., Prabhu, K. S., Shanmugakonar, M., Al-Naemi, H. A., Haris, M., Dermime, S., & Uddin, S. (Accepted/In press). RAS-mediated oncogenic signaling pathways in human malignancies. Seminars in Cancer Biology. https://doi.org/10.1016/j.semcancer.2018.03.001