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2017 ; 6
(2
): ä Nephropedia Template TP
gab.com Text
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English Wikipedia
Strange Bedfellows: Nuclear Factor, Erythroid 2-Like 2 (Nrf2) and
Hypoxia-Inducible Factor 1 (HIF-1) in Tumor Hypoxia
#MMPMID28383481
Toth RK
; Warfel NA
Antioxidants (Basel)
2017[Apr]; 6
(2
): ä PMID28383481
show ga
The importance of the tumor microenvironment for cancer progression and
therapeutic resistance is an emerging focus of cancer biology. Hypoxia, or low
oxygen, is a hallmark of solid tumors that promotes metastasis and represents a
significant obstacle to successful cancer therapy. In response to hypoxia, cancer
cells activate a transcriptional program that allows them to survive and thrive
in this harsh microenvironment. Hypoxia-inducible factor 1 (HIF-1) is considered
the main effector of the cellular response to hypoxia, stimulating the
transcription of genes involved in promoting angiogenesis and altering cellular
metabolism. However, growing evidence suggests that the cellular response to
hypoxia is much more complex, involving coordinated signaling through stress
response pathways. One key signaling molecule that is activated in response to
hypoxia is nuclear factor, erythroid 2 like-2 (Nrf2). Nrf2 is a transcription
factor that controls the expression of antioxidant-response genes, allowing the
cell to regulate reactive oxygen species. Nrf2 is also activated in various
cancer types due to genetic and epigenetic alterations, and is associated with
poor survival and resistance to therapy. Emerging evidence suggests that
coordinated signaling through Nrf2 and HIF-1 is critical for tumor survival and
progression. In this review, we discuss the distinct and overlapping roles of
HIF-1 and Nrf2 in the cellular response to hypoxia, with a focus on how targeting
Nrf2 could provide novel chemotherapeutic modalities for treating solid tumors.