NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors

Experimental & Molecular Medicine
Ga Young LeeJong-Wan Park

Abstract

Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA. In addition, NDRG3 functionally inhibited HIF-1 by dissociating the coactivator p300 from HIF-1α. Accordingly, NDRG3 may fine-tune the HIF-1 signaling pathway to cope with long-term hypoxia. Of the diverse effects of HIF-1α on cancer progression, hypoxia-induced cell migration was investigated. In transwell chambers, NDRG3 negatively regulated the migration and invasion of prostate cancer cells under hypoxia. An informatics analysis using Gene Expression Omnibus (GEO) revealed that NDRG3 downregulation is associated with prostate cancer metastasis and high expression of HIF-1 downstream genes. In cancer tissue arrays, NDRG3 expression was lower in prostate cancer tissues ...Continue Reading

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·L E HuangH F Bunn
Dec 28, 1999·Annual Review of Cell and Developmental Biology·G L Semenza
Aug 23, 2001·Trends in Molecular Medicine·G L Semenza
Feb 2, 2002·Science·David LandoMurray L Whitelaw
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Sep 26, 2003·The American Journal of Pathology·Tsutomu ImaiIkuo Konishi
May 4, 2004·Nature Reviews. Molecular Cell Biology·Christopher J Schofield, Peter J Ratcliffe
Sep 29, 2004·Journal of Clinical Pathology·A E Greijer, E van der Wall
Jan 4, 2007·The Journal of Biological Chemistry·Karen BlockHanna E Abboud
Jun 7, 2007·International Journal of Cancer. Journal International Du Cancer·Sanjeev ShuklaSanjay Gupta
Feb 26, 2008·Nature Cell Biology·Muh-Hwa YangKou-Juey Wu
Mar 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Amandine GinouvèsEdurne Berra
May 24, 2008·Molecular Cell·William G Kaelin, Peter J Ratcliffe
Nov 1, 2008·International Journal of Cancer. Journal International Du Cancer·Weiqun WangRunsheng Li
Sep 2, 2009·Molecular and Cellular Biology·Yoji Andrew MinamishimaWilliam G Kaelin
Jul 6, 2010·Biochemical and Biophysical Research Communications·Hyun-Woo ShinJong-Wan Park
Apr 22, 2015·Cell·Dong Chul LeeYoung Il Yeom
Dec 10, 2015·Scientific Reports·Miguel A S CavadasCormac T Taylor
Mar 23, 2017·Future Oncology·Mehrdad Asghari EstiarKeivan Majidzadeh-A

❮ Previous
Next ❯

Citations

Feb 26, 2020·Journal of Experimental & Clinical Cancer Research : CR·Yiyang JiaChengshi Quan
Apr 24, 2021·Asian Journal of Psychiatry·Dhruva IthalSanjeev Jain

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE6919

Methods Mentioned

BETA
PCR
two-hybrid
immunoprecipitation
co-immunoprecipitation
ubiquitination

Software Mentioned

GraphPad Prism
SigmaPlot
Excel
ImageJ
GSEA

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.