Abstract
Focal adhesion kinase (FAK) is implicated in cancer cell survival, proliferation and migration. Expression of FAK expression is elevated and associated with tumor progression and metastasis in various tumors, including hepatocellular carcinoma (HCC). Increased 14-3-3ε expression is shown to be a potential prognostic factor to predict higher risk of distant metastasis and worse overall survival in HCC. The aim of this study is to investigate whether FAK is associated or regulated by 14-3-3ε to modulate tumor progression in HCC. In this study, 114 primary HCC tumors including 34 matched metastatic tumors were subjected to immunohistochemistry analysis of FAK and 14-3-3ε expression. Overexpression of FAK was significantly associated with increased risk of extrahepatic metastasis (p=0.027) and reduced 5-year overall survival rate (p=0.017). A significant correlation of FAK and 14-3-3ε expression was observed in primary tumor (p<0.001) and also metastatic tumors. Furthermore, overexpression of 14-3-3ε induced FAK expression and promoter activity which were determined by Western blotting analysis and luciferase-reporter assay. Moreover, 14-3-3ε enhanced NFκB activation and increased nuclear translocation of NFκB. Results from chromatin immunoprecipitation assay revealed that 14-3-3ε induced NFκB binding on FAK promoter region. These findings suggest that FAK expression is correlated with and upregulated by 14-3-3ε via activation of NFκB. Target to suppress or inactivate FAK alone, or combine with 14-3-3ε is thus considered as the potential therapeutic strategy for preventing HCC tumor progression.
Keywords: 14-3-3ε, Focal adhesion kinase, Hepatocellular carcinoma, Metastasis, NFκB, Survival
Anti-Cancer Agents in Medicinal Chemistry
Title:Upregulation of Focal Adhesion Kinase by 14-3-3ε via NFκB Activation in Hepatocellular Carcinoma
Volume: 13 Issue: 4
Author(s): Bor-Sheng Ko, Yee-Jee Jan, Tzu-Ching Chang, Shu-Man Liang, Shyh-Chang Chen, Tzu-An Liu, Yao-Ming Wu, John Wang and Jun-Yang Liou
Affiliation:
Keywords: 14-3-3ε, Focal adhesion kinase, Hepatocellular carcinoma, Metastasis, NFκB, Survival
Abstract: Focal adhesion kinase (FAK) is implicated in cancer cell survival, proliferation and migration. Expression of FAK expression is elevated and associated with tumor progression and metastasis in various tumors, including hepatocellular carcinoma (HCC). Increased 14-3-3ε expression is shown to be a potential prognostic factor to predict higher risk of distant metastasis and worse overall survival in HCC. The aim of this study is to investigate whether FAK is associated or regulated by 14-3-3ε to modulate tumor progression in HCC. In this study, 114 primary HCC tumors including 34 matched metastatic tumors were subjected to immunohistochemistry analysis of FAK and 14-3-3ε expression. Overexpression of FAK was significantly associated with increased risk of extrahepatic metastasis (p=0.027) and reduced 5-year overall survival rate (p=0.017). A significant correlation of FAK and 14-3-3ε expression was observed in primary tumor (p<0.001) and also metastatic tumors. Furthermore, overexpression of 14-3-3ε induced FAK expression and promoter activity which were determined by Western blotting analysis and luciferase-reporter assay. Moreover, 14-3-3ε enhanced NFκB activation and increased nuclear translocation of NFκB. Results from chromatin immunoprecipitation assay revealed that 14-3-3ε induced NFκB binding on FAK promoter region. These findings suggest that FAK expression is correlated with and upregulated by 14-3-3ε via activation of NFκB. Target to suppress or inactivate FAK alone, or combine with 14-3-3ε is thus considered as the potential therapeutic strategy for preventing HCC tumor progression.
Export Options
About this article
Cite this article as:
Ko Bor-Sheng, Jan Yee-Jee, Chang Tzu-Ching, Liang Shu-Man, Chen Shyh-Chang, Liu Tzu-An, Wu Yao-Ming, Wang John and Liou Jun-Yang, Upregulation of Focal Adhesion Kinase by 14-3-3ε via NFκB Activation in Hepatocellular Carcinoma, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (4) . https://dx.doi.org/10.2174/1871520611313040004
DOI https://dx.doi.org/10.2174/1871520611313040004 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Aceruloplasminemia
Current Drug Targets A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1
Current Cancer Drug Targets Identification of Novel Drug Targets for Angiostatic Cancer Therapy; It Takes Two to Tango
Current Pharmaceutical Design The Potential Role of Peritumoral Apparent Diffusion Coefficient Evaluation in Differentiating Glioblastoma and Solitary Metastatic Lesions of the Brain
Current Medical Imaging Folate-modified Graphene Oxide as the Drug Delivery System to Load Temozolomide
Current Pharmaceutical Biotechnology Modified cAMP Derivatives: Powerful Tools in Heart Research
Current Medicinal Chemistry Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy
Current Medicinal Chemistry Evasion of Ribonuclease Inhibitor as a Determinant of Ribonuclease Cytotoxicity
Current Pharmaceutical Biotechnology Medicinal Chemistry of Indolylglyoxylamide TSPO High Affinity Ligands with Anxiolytic-Like Effects
Current Topics in Medicinal Chemistry MMPs in Ovarian Cancer as Therapeutic Targets
Anti-Cancer Agents in Medicinal Chemistry Effects of Iron Chelation in Osteosarcoma
Current Cancer Drug Targets Targeted Therapy Options for Treatment of Bone Metastases; Beyond Bisphosphonates
Current Pharmaceutical Design The Role of microRNA in Ischemic and Hemorrhagic Stroke
Current Drug Delivery A Closer Look at α-Secretase
Current Alzheimer Research The Heat Shock Protein 90 Chaperone Complex: An Evolving Therapeutic Target
Current Cancer Drug Targets Contribution of Inflammation to Fat Redistribution and Metabolic Disturbances in HIV-1 Infected Patients
Current Pharmaceutical Design microRNA as Biomarkers and Regulator of Cardiovascular Development and Disease
Current Pharmaceutical Design Current Advances in Vehicles for Brain Gene Delivery
Current Gene Therapy Alpha-Emitters for Immuno-Therapy: A Review of Recent Developments from Chemistry to Clinics
Current Topics in Medicinal Chemistry 7-Keto-Δ5-Steroids: Key-Molecules Owning Particular Biological and Chemical Interest
Mini-Reviews in Medicinal Chemistry