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Title: Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma

Journal Article · · Journal of Cellular and Molecular Medicine
DOI:https://doi.org/10.1111/jcmm.12620· OSTI ID:1213428
 [1];  [2];  [3];  [4];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of California, San Francisco, CA (United States)
  2. Univ. of California, San Francisco, CA (United States); Tongji Univ. School of Medicine, Shanghai (China)
  3. Univ. of California, San Francisco, CA (United States); Chang Gung Memorial Hospital, Taoyuan (Taiwan)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
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Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
NIH Grant R01 CA140654-01A1
OSTI ID:
1213428
Journal Information:
Journal of Cellular and Molecular Medicine, Journal Name: Journal of Cellular and Molecular Medicine; ISSN 1582-1838
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

References (25)

Role of Hedgehog Signaling in Malignant Pleural Mesothelioma journal June 2012
Gli as a Novel Therapeutic Target in Malignant Pleural Mesothelioma journal March 2013
Gli1 inhibition induces cell-cycle arrest and enhanced apoptosis in brain glioma cell lines journal December 2009
Targeting the mTOR-DEPTOR Pathway by CRL E3 Ubiquitin Ligases: Therapeutic Application journal May 2012
WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase journal April 2008
PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex journal September 2008
Molecular mechanisms of epithelial–mesenchymal transition journal February 2014
Lung tumourigenesis in a conditional Cul4A transgenic mouse model : Cul4A in lung tumourigenesis journal May 2014
Cullin-RING Ligases as Attractive Anti-cancer Targets journal April 2013
CUL4A Induces Epithelial–Mesenchymal Transition and Promotes Cancer Metastasis by Regulating ZEB1 Expression journal December 2013
CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases journal February 2014
Comparative genomic hybridization of squamous cell carcinoma of the esophagus: The possible involvement of theDP1 gene in the 13q34 amplicon journal April 1999
The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing journal September 2008
Regulation of Wnt Signaling and Embryo Patterning by an Extracellular Sulfatase journal August 2001
TFDP1, CUL4A, andCDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas journal June 2002
Crosstalk between hedgehog and other signaling pathways as a basis for combination therapies in cancer journal July 2014
Cul4A is an oncogene in malignant pleural mesothelioma journal February 2011
The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and other malignancies journal September 2013
Identification of Novel Amplification Gene Targets in Mouse and Human Breast Cancer at a Syntenic Cluster Mapping to Mouse ch8A1 and Human ch13q34 journal April 2007
The Crosstalk of mTOR/S6K1 and Hedgehog Pathways journal March 2012
REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A–DDB1 ubiquitin ligase journal June 2009
GLI inhibitor GANT-61 diminishes embryonal and alveolar rhabdomyosarcoma growth by inhibiting Shh/AKT-mTOR axis journal October 2014
Perifosine Inhibits Mammalian Target of Rapamycin Signaling through Facilitating Degradation of Major Components in the mTOR Axis and Induces Autophagy journal November 2009
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer journal April 2009
A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro journal April 1997

Cited By (4)

The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer journal December 2018
Switching off malignant mesothelioma: exploiting the hypoxic microenvironment journal January 2017
The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh journal May 2017
Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells journal March 2016

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
malignant pleural mesothelioma
Cul4A
Gli1
hedgehog signalling
mTOR