Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1)

Ivraj Singh Sandhu, Nicholas James Maksim, Eva Alice Amouzougan, Bryce Wilson Gallion, Anthony L J Raviele, Aikseng Ooi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The nuclear erythroid 2-like 2 transcription factor (NRF2), is a major regulator of cellular redox balance. Although NRF2 activation is generally regarded as beneficial to human health, recent studies have identified that sustained NRF2 activation is over-represented in many cancers. This raises the question regarding the role of NRF2 activation in the development and progression of those cancers. This review focuses on the mechanisms and the effects of NRF2 activation in two hereditary cancer predisposition syndromes: hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary tyrosinemia type 1 (HT1). Because the cancer initiating mutations in these hereditary syndromes are well defined, they offer a unique opportunity to explore the roles of NRF2 activation in the early stages of carcinogenesis. Over the years, a variety of approaches have been utilized to study the biology of HLRCC and HT1. In HLRCC, in vitro studies have demonstrated the importance of NRF2 activation in sustaining cancer cell proliferation. In the mouse model of HT1 however, NRF2 activation seems to protect cells from malignant transformation. In both HT1 and HLRCC, NRF2 activation promotes the clearance of electrophilic metabolites, enabling cells to survive cancer-initiating mutations. Biological insights gained from the hereditary syndromes' studies may shed light on to the roles of NRF2 activation in sporadic tumours.

Original languageEnglish (US)
Pages (from-to)650-656
Number of pages7
JournalBiochemical Society Transactions
Volume43
DOIs
StatePublished - Aug 1 2015

Fingerprint

Tyrosinemias
Chemical activation
Neoplasms
Hereditary Neoplastic Syndromes
Mutation
Oxidation-Reduction
Hereditary leiomyomatosis and renal cell cancer
Carcinogenesis
Transcription Factors
Cell Proliferation
Cell proliferation
Metabolites
Tumors
Health

Keywords

  • Fumarate hydratase (FH)
  • Fumarylacetoacetate hydrolase gene (FAH)
  • Hereditary leiomyomatosis and renal cell cancer (HLRCC)
  • Hereditary tyrosinemia type 1
  • Kelch-like ECH-associated protein 1 (KEAP1)
  • Nuclear erythroid 2-like 2 transcription factor (NRF2)

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1). / Sandhu, Ivraj Singh; Maksim, Nicholas James; Amouzougan, Eva Alice; Gallion, Bryce Wilson; Raviele, Anthony L J; Ooi, Aikseng.

In: Biochemical Society Transactions, Vol. 43, 01.08.2015, p. 650-656.

Research output: Contribution to journalArticle

Sandhu, Ivraj Singh ; Maksim, Nicholas James ; Amouzougan, Eva Alice ; Gallion, Bryce Wilson ; Raviele, Anthony L J ; Ooi, Aikseng. / Sustained NRF2 activation in hereditary leiomyomatosis and renal cell cancer (HLRCC) and in hereditary tyrosinemia type 1 (HT1). In: Biochemical Society Transactions. 2015 ; Vol. 43. pp. 650-656.
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