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ERKs in Cancer: Friends or Foes?

Deschênes-Simard, Xavier, Kottakis, Filippos, Meloche, Sylvain, Ferbeyre, Gerardo·2014·Cancer Research
DOI 10.1158/0008-5472.can-13-2381
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Abstract

The extracellular signal–regulated kinase ERK1 and ERK2 (ERK1/2) cascade regulates a variety of cellular processes by phosphorylating multiple target proteins. The outcome of its activation ranges from stimulation of cell survival and proliferation to triggering tumor suppressor responses such as cell differentiation, cell senescence, and apoptosis. This pathway is intimately linked to cancer as several of its upstream activators are frequently mutated in human disease and are shown to accelerate tumorigenesis when engineered in the mouse genome. However, measurement of activated ERKs in human cancers or mouse models does not always support a role in tumorigenesis, and data consistent with a role in tumor suppression have been reported as well. The intensity of ERK signaling, negative feedback loops that regulate the pathway, and cross-talks with other signaling pathways, seem to be of primary importance in determining the final cellular outcome. Cell senescence, a putative tumor-suppression mechanism, depends on high-intensity ERK signals that trigger phosphorylation-dependent protein degradation of multiple proteins required for cell-cycle progression. This response may be circumvented during carcinogenesis by a variety of mechanisms, some of them yet to be discovered, which in essence turn ERK functions from tumor suppression to tumor promotion. The use of pharmacologic inhibitors targeting this pathway must be carefully evaluated so they are applied to cases in which ERKs are mainly oncogenic. Cancer Res; 74(2); 412–9. ©2014 AACR.

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  • Fine-tuning of MEK/ERK pathway activation by natural bioactive compounds, such as flavonoids, appears to promote physiological responses of gene transcription/translation and cell growth/survival and, in turn, advance human health as neuroprotectants and cognitive enhancers.

    “Although sustained hyperactivation of MEK/ERK signaling is a prerequisite for malignant transformation or progression, the fine-tuning of this pathway activation by natural bioactive compounds, such as flavonoids, appears to promote physiological responses of gene transcription/translation and cell growth/survival and, in turn, advance human health as neuroprotectants and cognitive enhancers.48–51”

    From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [50]

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Metadata

Authors
Deschênes-Simard, X., Kottakis, F., Meloche, S., & Ferbeyre, G.
Affiliations
Authors' Affiliations: 1Département de Biochimie et Médecine Moléculaire; 2Department of Pharmacology and Program in Molecular Biology, Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montréal, Québec, Canada; and 3Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2014-01-15
Volume
74
Issue
2
Pages
412-419
ISSN
  • 0008-5472
  • 1538-7445
DOI
10.1158/0008-5472.can-13-2381
Cited by
186
References
18
Language
en

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