Abstract
Focal Adhesion Kinase (FAK) plays an important role in cancer cell survival. Previous microarray gene profiling study detected inverse regulation between expression of thioredoxin-interacting protein (TXNIP) and FAK, where down-regulation of FAK by siRNA in MCF-7 cells caused up-regulation of TXNIP mRNA level, and in contrast up-regulation of doxycyclin- induced FAK caused repression of TXNIP. In the present report, we show that overexpression of FAK in MCF-7 cells repressed TXNIP promoter activity. Treatment of MCF-7 cells with 1alpha, 25-dihydroxyvitamin D3 (1,25D) down-regulated endogenous FAK and up-regulated TXNIP protein level, and treatment with 5-FU decreased FAK protein expression and up-regulated TXNIP protein expression in 293 cells. Moreover, silencing of FAK with siRNA increased TXNIP protein expression, while overexpression of FAK inhibited TXNIP protein expression in 293 cells. In addition, treatment of DBTRG glioblastoma cells with FAK inhibitor Y15 increased TXNIP mRNA, decreased cancer cell viability and increased apoptosis. These results for the first time demonstrate FAK-regulated TXNIP expression which is important for apoptotic, survival and oxidative stress signaling pathways in cancer cells.
Keywords: Apoptosis, brain cancer, breast cancer, focal adhesion kinase, thioredoxin-interacting protein.
Anti-Cancer Agents in Medicinal Chemistry
Title:Focal Adhesion Kinase Regulates Expression of Thioredoxin-interacting Protein (TXNIP) in Cancer Cells
Volume: 14 Issue: 1
Author(s): Baotran Ho, Grace Huang and Vita M. Golubovskaya
Affiliation:
Keywords: Apoptosis, brain cancer, breast cancer, focal adhesion kinase, thioredoxin-interacting protein.
Abstract: Focal Adhesion Kinase (FAK) plays an important role in cancer cell survival. Previous microarray gene profiling study detected inverse regulation between expression of thioredoxin-interacting protein (TXNIP) and FAK, where down-regulation of FAK by siRNA in MCF-7 cells caused up-regulation of TXNIP mRNA level, and in contrast up-regulation of doxycyclin- induced FAK caused repression of TXNIP. In the present report, we show that overexpression of FAK in MCF-7 cells repressed TXNIP promoter activity. Treatment of MCF-7 cells with 1alpha, 25-dihydroxyvitamin D3 (1,25D) down-regulated endogenous FAK and up-regulated TXNIP protein level, and treatment with 5-FU decreased FAK protein expression and up-regulated TXNIP protein expression in 293 cells. Moreover, silencing of FAK with siRNA increased TXNIP protein expression, while overexpression of FAK inhibited TXNIP protein expression in 293 cells. In addition, treatment of DBTRG glioblastoma cells with FAK inhibitor Y15 increased TXNIP mRNA, decreased cancer cell viability and increased apoptosis. These results for the first time demonstrate FAK-regulated TXNIP expression which is important for apoptotic, survival and oxidative stress signaling pathways in cancer cells.
Export Options
About this article
Cite this article as:
Ho Baotran, Huang Grace and Golubovskaya M. Vita, Focal Adhesion Kinase Regulates Expression of Thioredoxin-interacting Protein (TXNIP) in Cancer Cells, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (1) . https://dx.doi.org/10.2174/18715206113139990140
DOI https://dx.doi.org/10.2174/18715206113139990140 |
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
-
Molecular Aspects of Intestinal Radiation-Induced Fibrosis
Current Molecular Medicine Overview of Prostate Biomarkers as Potential Targets for Immunotherapy
Current Cancer Therapy Reviews Nano Conjugated PLGA-Chlorambucil: Synthesis In Vitro Anti Non- Hodgkin's Lymphoma Cellular Assay
Letters in Drug Design & Discovery The Significance of COX-2 and COX-2 Inhibitors in Liver Fibrosis and Liver Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Momordica balsamina: A Medicinal and Neutraceutical Plant for Health Care Management
Current Pharmaceutical Biotechnology Cyclooxygenases Regulation by Estradiol on Endothelium
Current Pharmaceutical Design Ocular Toxicities in Cancer Therapy: Still Overlooked
Current Cancer Therapy Reviews The Therapeutic Potential of Gallium-Based Complexes in Anti-Tumor Drug Design
Letters in Drug Design & Discovery Clinically Relevant Genetic Variations in Drug Metabolizing Enzymes
Current Drug Metabolism Eco-friendly Synthesis of Pyrido[2,3-d]pyrimidine Analogs and Their Anticancer and Tyrosine Kinase Inhibition Activities
Anti-Cancer Agents in Medicinal Chemistry Radiobromine-Labelled Tracers for Positron Emission Tomography: Possibilities and Pitfalls
Current Radiopharmaceuticals Bioconjugation of Polymers: A Novel Platform for Targeted Drug Delivery
Current Pharmaceutical Design Gamma-Oryzanol – A Multi-Purpose Steryl Ferulate
Current Nutrition & Food Science Fluoroquinolones Prophylaxis of Bacterial Infections in Neutropenic Patients: Time to Re-Evaluate
Current Cancer Therapy Reviews Inflammation as a Therapeutic Target in Acute Ischemic Stroke Treatment
Current Topics in Medicinal Chemistry Biological Activities, Mechanisms of Action and Biomedical Prospect of the Antitumor Ether Phospholipid ET-18-OCH3 (Edelfosine), A Proapoptotic Agent in Tumor Cells
Current Drug Metabolism Sirtuins: Possible Clinical Implications in Cardio and Cerebrovascular Diseases
Current Drug Targets The Physiological Characteristics and Transcytosis Mechanisms of the Blood-Brain Barrier (BBB)
Current Pharmaceutical Biotechnology The Role of Biologically Active Ingredients from Chinese Herbal Medicines in the Regulation of Autophagy in Treating Cardiovascular Diseases and Other Chronic Diseases
Current Pharmaceutical Design Targeting CXCL12/CXCR4 Axis in Tumor Immunotherapy
Current Medicinal Chemistry