Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10

Journal Article · · Cancers (Basel)
 [1];  [2];  [3];  [2];  [2];  [2];  [4];  [4];  [5];  [4];  [6]
  1. Chang Gung Memorial Hospital, Chiayi (Taiwan); Chang Gung University, Taoyuan (Taiwan); Chang Gung University of Science and Technology, Chiayi (Taiwan)
  2. Chang Gung Memorial Hospital, Chiayi (Taiwan)
  3. Buddhist Tzu Chi Medical Foundation, Chiayi (Taiwan)
  4. Univ. of California, San Francisco, CA (United States)
  5. Chang Gung University, Taoyuan (Taiwan)
  6. Chang Gung University, Taoyuan (Taiwan); Chang Gung Memorial Hospital, Taoyuan (Taiwan)
+ Show Author Affiliations
Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
Chang Gung Memorial Hospital; National Science Council, Taiwan; USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1637291
Journal Information:
Cancers (Basel), Journal Name: Cancers (Basel) Journal Issue: 5 Vol. 11; ISSN CANCCT; ISSN 2072-6694
Publisher:
MDPICopyright Statement
Country of Publication:
United States
Language:
English

References (42)

Transgenic mice for cre-inducible overexpression of the Cul4A gene journal March 2011
Identification of annexin A1 as a novel substrate for E6AP-mediated ubiquitylation journal April 2009
The role of annexins in tumour development and progression journal October 2008
Simvastatin Up-Regulates Annexin A10 That Can Inhibit the Proliferation, Migration, and Invasion in Androgen-Independent Human Prostate Cancer Cells: Simvastatin Up-Regulates Annexin A10 journal November 2016
CUL4A Abrogation Augments DNA Damage Response and Protection against Skin Carcinogenesis journal May 2009
Down-Regulation of Annexin A10 in Hepatocellular Carcinoma Is Associated with Vascular Invasion, Early Recurrence, and Poor Prognosis in Synergy with p53 Mutation journal May 2002
Low ANXA10 expression is associated with disease aggressiveness in bladder cancer journal October 2011
VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation journal March 2008
Proliferation defects and genome instability in cells lacking Cul4A journal May 2009
Ubiquitin-protein ligase E3C promotes glioma progression by mediating the ubiquitination and degrading of Annexin A7 journal June 2015
Cullin-4A·DNA Damage-binding Protein 1 E3 Ligase Complex Targets Tumor Suppressor RASSF1A for Degradation during Mitosis journal January 2011
Dysregulation of CUL4A and CUL4B Ubiquitin Ligases in Lung Cancer journal December 2016
CDK Inhibitor p21 Is Degraded by a Proliferating Cell Nuclear Antigen-coupled Cul4-DDB1 Cdt2 Pathway during S Phase and after UV Irradiation journal August 2008
Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene: Lung tumors in Cul4A transgenic mice journal June 2015
Cul4A is an oncogene in malignant pleural mesothelioma journal February 2011
Cul4A Physically Associates with MDM2 and Participates in the Proteolysis of p53 journal November 2004
CUL4A Induces Epithelial–Mesenchymal Transition and Promotes Cancer Metastasis by Regulating ZEB1 Expression journal December 2013
Knockdown of CUL4A inhibits invasion and induces apoptosis in osteosarcoma cells journal June 2015
Cul4A targets p27 for degradation and regulates proliferation, cell cycle exit, and differentiation during erythropoiesis journal June 2006
Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis journal July 2008
CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR journal January 2014
Comprehensive characterization of the DNA amplification at 13q34 in human breast cancer reveals TFDP1 and CUL4A as likely candidate target genes journal December 2009
SCFβ-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration journal November 2013
Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer proliferation and invasion by regulating the Hippo signaling pathway journal January 2016
CUL4A promotes proliferation and metastasis of colorectal cancer cells by regulating H3K4 trimethylation in epithelial–mesenchymal transition journal January 2017
Investigation of the role of cullin 4A overexpression in human liver cancer journal June 2018
Knockdown of Cul4A increases chemosensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells journal October 2015
Reduced expression and homozygous deletion of annexin A10 in gastric carcinoma journal October 2009
Down-Regulation of Annexin A10 in Hepatocellular Carcinoma Is Associated with Vascular Invasion, Early Recurrence, and Poor Prognosis in Synergy with p53 Mutation journal May 2002
Overexpression of Annexin A2 Is Associated with Abnormal Ubiquitination in Breast Cancer journal June 2012
Histone H3 and H4 Ubiquitylation by the CUL4-DDB-ROC1 Ubiquitin Ligase Facilitates Cellular Response to DNA Damage journal May 2006
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer journal April 2009
Function and regulation of cullin–RING ubiquitin ligases journal January 2005
Cullin-4A·DNA Damage-binding Protein 1 E3 Ligase Complex Targets Tumor Suppressor RASSF1A for Degradation during Mitosis journal January 2011
Dysregulation of CUL4A and CUL4B Ubiquitin Ligases in Lung Cancer journal December 2016
CDK Inhibitor p21 Is Degraded by a Proliferating Cell Nuclear Antigen-coupled Cul4-DDB1 Cdt2 Pathway during S Phase and after UV Irradiation journal August 2008
Differential expression of S100A2 and S100A4 in lung adenocarcinomas: Clinicopathological significance, relationship to p53 and identification of their target genes journal December 2005
Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells journal March 2016
Cul4A Physically Associates with MDM2 and Participates in the Proteolysis of p53 journal November 2004
CUL4A Induces Epithelial–Mesenchymal Transition and Promotes Cancer Metastasis by Regulating ZEB1 Expression journal December 2013
Histone H3 and H4 Ubiquitylation by the CUL4-DDB-ROC1 Ubiquitin Ligase Facilitates Cellular Response to DNA Damage text January 2006
CUL4A promotes proliferation and metastasis of colorectal cancer cells by regulating H3K4 trimethylation in epithelial–mesenchymal transition journal January 2017

Figures / Tables (6)

Figure 1(p. 7)figure Figure 1
Figure 2(p. 7)figure Figure 2
Figure 3(p. 8)figure Figure 3
Figure 4(p. 10)figure Figure 4
Figure 5(p. 11)figure Figure 5
Figure 6(p. 12)figure Figure 6

Similar Records

CUL4A overexpression enhances lung tumor growth and sensitizes lung cancer cells to Erlotinib via transcriptional regulation of EGFR
Journal Article · Thu Nov 20 19:00:00 EST 2014 · Molecular Cancer · OSTI ID:1257383
CUL4A functions as an oncogene in ovarian cancer and is directly regulated by miR-494
Journal Article · Thu Nov 24 23:00:00 EST 2016 · Biochemical and Biophysical Research Communications · OSTI ID:22696714
Down-regulation of TRAF4 targeting RSK4 inhibits proliferation, invasion and metastasis in breast cancer xenografts
Journal Article · Fri Jun 15 00:00:00 EDT 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23125180

Related Subjects

60 APPLIED LIFE SCIENCES
ANXA10
Cul4A
lung cancer
metastasis