Cited by 62Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

The effects of mutant Ras proteins on the cell signalome

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Takács, Tamás, Kudlik, Gyöngyi, Kurilla, Anita, Szeder, Bálint, Buday, László, Vas, Virag·2020·Cancer and Metastasis Reviews

Abstract

The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells.

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  • KRAS activation leads to downstream signaling of three major pathways: MAPK, PI3K-AKT-mTOR, and TIAM1-RAC/RAL.

    “KRAS activation leads to downstream signaling of three major pathways: the MAP kinase pathway, PI3K-AKT-mTOR pathway, and the tumour invasion and metastasis-inducing protein 1 (TIAM1-RAC) and RAS-related protein (RAL) pathways (Fig. 3).”

    From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [35]

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Authors
Takács, T., Kudlik, G., Kurilla, A., Szeder, B., Buday, L., & Vas, V.
Affiliations
  • Institute of Molecular Life Sciences (HU)
  • Semmelweis University (HU)
Venue
Cancer and Metastasis Reviews
Published
2020-07-09
Volume
39
Issue
4
Pages
1051-1065
ISSN
  • 0167-7659 (ISSN-L)
  • 1573-7233
OpenAlex
W3042072586
Cited by
62
References
129
Citations by year
2026: 3 · 2025: 8 · 2024: 15 · 2023: 19 · 2022: 4 · 2021: 11 · 2020: 1 · 2016: 1
FWCI
0.86
Type
journal article
Language
en
Open access
Locations
  • Cancer and Metastasis Reviews (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
  • Semmelweis University Repository (Semmelweis University) (submittedVersion)
Funders
ELKH Research Centre for Natural Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
oncogenic Ras, RAS mutations, cancer pathways, Raf/MEK/ERK pathway, PI3K/AKT/mTOR pathway, microRNA regulation, cancer stem cells, signal transduction, signaling crosstalk, carcinogenesis
MeSH terms
Animals, Humans, Mutation, Neoplasms, Signal Transduction, Proto-Oncogene Proteins p21(ras)

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