Molecular pathways: the role of NR4A orphan nuclear receptors in cancer.

Hdl Handle:
http://hdl.handle.net/10147/264355
Title:
Molecular pathways: the role of NR4A orphan nuclear receptors in cancer.
Authors:
Mohan, Helen M; Aherne, Carol M; Rogers, Ailin C; Baird, Alan W; Winter, Des C; Murphy, Evelyn P
Affiliation:
UCD Veterinary Sciences Centre, University College Dublin, Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin, Ireland. helen.mohan@gmail.com
Citation:
Molecular pathways: the role of NR4A orphan nuclear receptors in cancer. 2012, 18 (12):3223-8 Clin. Cancer Res.
Journal:
Clinical cancer research : an official journal of the American Association for Cancer Research
Issue Date:
15-Jun-2012
URI:
http://hdl.handle.net/10147/264355
DOI:
10.1158/1078-0432.CCR-11-2953
PubMed ID:
22566377
Abstract:
Nuclear receptors are of integral importance in carcinogenesis. Manipulation of classic ligand-activated nuclear receptors, such as estrogen receptor blockade in breast cancer, is an important established cancer therapy. Orphan nuclear receptors, such as nuclear family 4 subgroup A (NR4A) receptors, have no known natural ligand(s). These elusive receptors are increasingly recognized as molecular switches in cell survival and a molecular link between inflammation and cancer. NR4A receptors act as transcription factors, altering expression of downstream genes in apoptosis (Fas-ligand, TRAIL), proliferation, DNA repair, metabolism, cell migration, inflammation (interleukin-8), and angiogenesis (VEGF). NR4A receptors are modulated by multiple cell-signaling pathways, including protein kinase A/CREB, NF-κB, phosphoinositide 3-kinase/AKT, c-jun-NH(2)-kinase, Wnt, and mitogen-activated protein kinase pathways. NR4A receptor effects are context and tissue specific, influenced by their levels of expression, posttranslational modification, and interaction with other transcription factors (RXR, PPAR-Υ). The subcellular location of NR4A "nuclear receptors" is also important functionally; novel roles have been described in the cytoplasm where NR4A proteins act both indirectly and directly on the mitochondria to promote apoptosis via Bcl-2. NR4A receptors are implicated in a wide variety of malignancies, including breast, lung, colon, bladder, and prostate cancer; glioblastoma multiforme; sarcoma; and acute and/or chronic myeloid leukemia. NR4A receptors modulate response to conventional chemotherapy and represent an exciting frontier for chemotherapeutic intervention, as novel agents targeting NR4A receptors have now been developed. This review provides a concise clinical overview of current knowledge of NR4A signaling in cancer and the potential for therapeutic manipulation.
Item Type:
Article
Language:
en
MeSH:
Animals; Apoptosis; Cell Movement; Cell Proliferation; DNA Repair; Humans; Inflammation; Neoplasms; Neovascularization, Pathologic; Nuclear Receptor Subfamily 4, Group A, Member 1; Signal Transduction; Transcription, Genetic
ISSN:
1078-0432

Full metadata record

DC FieldValue Language
dc.contributor.authorMohan, Helen Men_GB
dc.contributor.authorAherne, Carol Men_GB
dc.contributor.authorRogers, Ailin Cen_GB
dc.contributor.authorBaird, Alan Wen_GB
dc.contributor.authorWinter, Des Cen_GB
dc.contributor.authorMurphy, Evelyn Pen_GB
dc.date.accessioned2013-01-07T14:36:03Z-
dc.date.available2013-01-07T14:36:03Z-
dc.date.issued2012-06-15-
dc.identifier.citationMolecular pathways: the role of NR4A orphan nuclear receptors in cancer. 2012, 18 (12):3223-8 Clin. Cancer Res.en_GB
dc.identifier.issn1078-0432-
dc.identifier.pmid22566377-
dc.identifier.doi10.1158/1078-0432.CCR-11-2953-
dc.identifier.urihttp://hdl.handle.net/10147/264355-
dc.description.abstractNuclear receptors are of integral importance in carcinogenesis. Manipulation of classic ligand-activated nuclear receptors, such as estrogen receptor blockade in breast cancer, is an important established cancer therapy. Orphan nuclear receptors, such as nuclear family 4 subgroup A (NR4A) receptors, have no known natural ligand(s). These elusive receptors are increasingly recognized as molecular switches in cell survival and a molecular link between inflammation and cancer. NR4A receptors act as transcription factors, altering expression of downstream genes in apoptosis (Fas-ligand, TRAIL), proliferation, DNA repair, metabolism, cell migration, inflammation (interleukin-8), and angiogenesis (VEGF). NR4A receptors are modulated by multiple cell-signaling pathways, including protein kinase A/CREB, NF-κB, phosphoinositide 3-kinase/AKT, c-jun-NH(2)-kinase, Wnt, and mitogen-activated protein kinase pathways. NR4A receptor effects are context and tissue specific, influenced by their levels of expression, posttranslational modification, and interaction with other transcription factors (RXR, PPAR-Υ). The subcellular location of NR4A "nuclear receptors" is also important functionally; novel roles have been described in the cytoplasm where NR4A proteins act both indirectly and directly on the mitochondria to promote apoptosis via Bcl-2. NR4A receptors are implicated in a wide variety of malignancies, including breast, lung, colon, bladder, and prostate cancer; glioblastoma multiforme; sarcoma; and acute and/or chronic myeloid leukemia. NR4A receptors modulate response to conventional chemotherapy and represent an exciting frontier for chemotherapeutic intervention, as novel agents targeting NR4A receptors have now been developed. This review provides a concise clinical overview of current knowledge of NR4A signaling in cancer and the potential for therapeutic manipulation.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Clinical cancer research : an official journal of the American Association for Cancer Researchen_GB
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCell Movement-
dc.subject.meshCell Proliferation-
dc.subject.meshDNA Repair-
dc.subject.meshHumans-
dc.subject.meshInflammation-
dc.subject.meshNeoplasms-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshNuclear Receptor Subfamily 4, Group A, Member 1-
dc.subject.meshSignal Transduction-
dc.subject.meshTranscription, Genetic-
dc.titleMolecular pathways: the role of NR4A orphan nuclear receptors in cancer.en_GB
dc.typeArticleen
dc.contributor.departmentUCD Veterinary Sciences Centre, University College Dublin, Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin, Ireland. helen.mohan@gmail.comen_GB
dc.identifier.journalClinical cancer research : an official journal of the American Association for Cancer Researchen_GB
dc.description.provinceLeinsteren
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