ArticleBiochemical pharmacology2011
ERK1/2 deactivation enhances cytoplasmic Nur77 expression level and improves the apoptotic effect of fenretinide in human liver cancer cells.
Article in Biochemical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- <p>KMO downregulation promotes hepatocellular carcinoma growth via 3‑HAA‑mediated mitochondrial mass and function imbalances</p>.International journal of oncology · 2026Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.Biochemistry research international · 2025Review
- Design, synthesis, and evaluation of novel benzoylhydrazone derivatives as Nur77 modulators with potent antitumor activity against hepatocellular carcinoma.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- MAPK signaling pathway-targeted marine compounds in cancer therapy.Journal of cancer research and clinical oncology · 2021Review
- Article
- RARβ acts as both an upstream regulator and downstream effector of miR-22, which epigenetically regulates NUR77 to induce apoptosis of colon cancer cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK.Oncotarget · 2017Article
- High expression of orphan nuclear receptor NR4A1 in a subset of ovarian tumors with worse outcome.Gynecologic oncology · 2016Article
- Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.Molecular cancer therapeutics · 2016Article
- Bile acids regulate nuclear receptor (Nur77) expression and intracellular location to control proliferation and apoptosis.Molecular cancer research : MCR · 2015Article
- Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation.Biochemical pharmacology · 2014Article
- Induction of Nur77-dependent apoptotic pathway by a coumarin derivative through activation of JNK and p38 MAPK.Carcinogenesis · 2014Article
- Accelerated partial hepatectomy-induced liver cell proliferation is associated with liver injury in Nur77 knockout mice.The American journal of pathology · 2014Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Fenretinide, a synthetic retinoid, is a promising anticancer agent based on many in vitro, animal, and chemoprevention clinical trial studies. However, cells such as HepG2 human liver cancer cells are resistant to the apoptotic effect of fenretinide. Previously, we have shown that fenretinide-induced apoptosis is Nur77 dependent, and the sensitivity of the cancer cells to fenretinide-induced apoptosis is positively associated with cytoplasmic enrichment of Nur77. The goal of current study was to identify means to modulate nuclear export of Nur77 in order to improve the efficacy of fenretinide. Fenretinide treatment deactivated ERK1/2 in Huh7 cells, but activated ERK1/2 in HepG2 cells, which was positively associated with the sensitivity of cells to the apoptotic effect of fenretinide. Neither fenretinide nor ERK1/2 inhibitor PD98059 alone could affect the survival of HepG2 cells, but the combination of both induced cell death and increased caspase 3/7 activity. In fenretinide sensitive Huh7 cells, activation of ERK1/2 by epidermal growth factor (EGF) prevented fenretinide-induced cell death and caspase 3/7 induction. In addition, modulation of ERK1/2 changed the intracellular localization of Nur77. Fenretinide/PD98059-induced cell death of HepG2 cell was positively associated with induction and cytoplasmic location as well as mitochondria enrichment of Nur77. The effect was specific for ERK1/2 because other mitogen activated protein kinases such as P38, Akt, and JNK did not have correlated changes in their phosphorylation levels. Taken together, the current study demonstrates that ERK1/2-modulated Nur77 intracellular location dictates the efficacy of fenretinide-induced apoptosis.
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