Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Angelo Sparaneo, Federico Pio Fabrizio, Lucia Anna Muscarella

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

The transcription factor Nrf2 (NF-E2 related factor 2) is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements) in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

Original languageEnglish
Article number7316492
JournalOxidative Medicine and Cellular Longevity
Volume2016
DOIs
Publication statusPublished - 2016

Fingerprint

NF-E2-Related Factor 2
Lung Neoplasms
Tumors
Genes
Crosstalk
Tissue homeostasis
Carcinogenesis
Antioxidant Response Elements
Neoplasms
Transcription factors
Cytoprotection
Cell proliferation
Biomarkers
Stem cells
Cell Differentiation
Cell Survival
Homeostasis
Transcription Factors
Up-Regulation
Antioxidants

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

Cite this

Nrf2 and Notch Signaling in Lung Cancer : Near the Crossroad. / Sparaneo, Angelo; Fabrizio, Federico Pio; Muscarella, Lucia Anna.

In: Oxidative Medicine and Cellular Longevity, Vol. 2016, 7316492, 2016.

Research output: Contribution to journalReview article

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