JRK is a positive regulator of β-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.

Pangon, L; Ng, I; Giry-Laterriere, M; Currey, N; Morgan, A; Benthani, F; Tran, PN; Al-Sohaily, S; Segelov, E; Parker, BL; Cowley, MJ; Wright, DC; St Heaps, L; Carey, L; Rooman, I; Kohonen-Corish, MRJ

JRK is a positive regulator of β-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.

Pangon, L Ng, I Giry-Laterriere, M Currey, N Morgan, A Benthani, F Tran, PN Al-Sohaily, S Segelov, E Parker, BL Cowley, MJ Wright, DC St Heaps, L Carey, L Rooman, I Kohonen-Corish, MRJ

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Publisher:: NATURE PUBLISHING GROUP
Publication Type:: Journal Article
Citation:: Oncogene, 2016, 35, (22), pp. 2834-2841
Issue Date:: 2016-06-02

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Field	Value	Language
dc.contributor.author	Pangon, L
dc.contributor.author	Ng, I
dc.contributor.author	Giry-Laterriere, M
dc.contributor.author	Currey, N
dc.contributor.author	Morgan, A
dc.contributor.author	Benthani, F
dc.contributor.author	Tran, PN
dc.contributor.author	Al-Sohaily, S
dc.contributor.author	Segelov, E
dc.contributor.author	Parker, BL
dc.contributor.author	Cowley, MJ
dc.contributor.author	Wright, DC
dc.contributor.author	St Heaps, L
dc.contributor.author	Carey, L
dc.contributor.author	Rooman, I
dc.contributor.author	Kohonen-Corish, MRJ
dc.date.accessioned	2022-08-20T07:50:09Z
dc.date.available	2015-07-24
dc.date.available	2022-08-20T07:50:09Z
dc.date.issued	2016-06-02
dc.identifier.citation	Oncogene, 2016, 35, (22), pp. 2834-2841
dc.identifier.issn	0950-9232
dc.identifier.issn	1476-5594
dc.identifier.uri	http://hdl.handle.net/10453/160562
dc.description.abstract	The loss of β-catenin inhibitory components is a well-established mechanism of carcinogenesis but β-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the β-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a β-catenin activator function, depletion of JRK in several cancer cell lines repressed β-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of β-catenin target genes and increased cell proliferation. This study shows that JRK is required for β-catenin hyperactivity regardless of the adenomatous polyposis coli/β-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	NATURE PUBLISHING GROUP
dc.relation	http://purl.org/au-research/grants/nhmrc/1020406
dc.relation.ispartof	Oncogene
dc.relation.isbasedon	10.1038/onc.2015.347
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.subject.mesh	Active Transport, Cell Nucleus
dc.subject.mesh	Base Sequence
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Nucleus
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Colonic Neoplasms
dc.subject.mesh	Computer Simulation
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Humans
dc.subject.mesh	Mutation
dc.subject.mesh	Nuclear Proteins
dc.subject.mesh	Oncogenes
dc.subject.mesh	Ovarian Neoplasms
dc.subject.mesh	Protein Domains
dc.subject.mesh	RNA-Binding Proteins
dc.subject.mesh	Transcription, Genetic
dc.subject.mesh	Up-Regulation
dc.subject.mesh	Wnt Signaling Pathway
dc.subject.mesh	beta Catenin
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Nucleus
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Colonic Neoplasms
dc.subject.mesh	Ovarian Neoplasms
dc.subject.mesh	Nuclear Proteins
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Transcription, Genetic
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Up-Regulation
dc.subject.mesh	Base Sequence
dc.subject.mesh	Active Transport, Cell Nucleus
dc.subject.mesh	Mutation
dc.subject.mesh	Oncogenes
dc.subject.mesh	Computer Simulation
dc.subject.mesh	Female
dc.subject.mesh	beta Catenin
dc.subject.mesh	Wnt Signaling Pathway
dc.subject.mesh	Protein Domains
dc.title	JRK is a positive regulator of β-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.
dc.type	Journal Article
utslib.citation.volume	35
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access	*
dc.date.updated	2022-08-20T07:50:05Z
pubs.issue	22
pubs.publication-status	Published
pubs.volume	35
utslib.citation.issue	22

Abstract:

The loss of β-catenin inhibitory components is a well-established mechanism of carcinogenesis but β-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the β-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a β-catenin activator function, depletion of JRK in several cancer cell lines repressed β-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of β-catenin target genes and increased cell proliferation. This study shows that JRK is required for β-catenin hyperactivity regardless of the adenomatous polyposis coli/β-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.

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http://hdl.handle.net/10453/160562