Abstract
Bortezomib, a modified dipeptidyl boronic acid, is a selective potent proteasome inhibitor that has been approved for clinical treatment of multiple myeloma and mantel cell lymphoma. Results from a growing number of basic studies and clinical trials reveal that bortezomib could be used to treat diverse types of solid tumors alone or in combination with other chemotherapeutic drugs. It has been shown that bortezomib transcriptionally suppresses focal adhesion kinase (FAK) expression by interrupting the nuclear factor kappa B (NFκB) pathway, which suggests that FAK could be a potential molecular target for bortezomib. Analysis of FAK promoter sequences revealed that FAK promoter harbors the NFκB and p53 binding domains. Further studies of FAK promoter activity, real-time PCR, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed that bortezomib inhibits NFκB binding on the FAK promoter, thereby reducing FAK expression. Thus, bortezomib could inhibit cancer cell growth and migration or invasion by repressing FAK expression. Since activation and overexpression of FAK has been implicated in the progression and invasion of malignant tumors, it is likely that targeting FAK with bortezomib is a potential strategy for preventing cancer metastasis. This review focuses on the molecular regulation of FAK and the potential clinical application of bortezomib.
Keywords: Bortezomib, Focal adhesion kinase, NFκB, p53, proteasome inhibitor, cancer treatment, Hepatocellular carcinoma, hematological malignancies, chromatin immunoprecipitation, EMSA, boronic acid, ubiquitin-proteasome, TRAIL, epoxomycin, actacystin
Anti-Cancer Agents in Medicinal Chemistry
Title: Focal Adhesion Kinase as a Therapeutic Target of Bortezomib
Volume: 10 Issue: 10
Author(s): Bor-Sheng Ko, Tzu-Ching Chang and Jun-Yang Liou
Affiliation:
Keywords: Bortezomib, Focal adhesion kinase, NFκB, p53, proteasome inhibitor, cancer treatment, Hepatocellular carcinoma, hematological malignancies, chromatin immunoprecipitation, EMSA, boronic acid, ubiquitin-proteasome, TRAIL, epoxomycin, actacystin
Abstract: Bortezomib, a modified dipeptidyl boronic acid, is a selective potent proteasome inhibitor that has been approved for clinical treatment of multiple myeloma and mantel cell lymphoma. Results from a growing number of basic studies and clinical trials reveal that bortezomib could be used to treat diverse types of solid tumors alone or in combination with other chemotherapeutic drugs. It has been shown that bortezomib transcriptionally suppresses focal adhesion kinase (FAK) expression by interrupting the nuclear factor kappa B (NFκB) pathway, which suggests that FAK could be a potential molecular target for bortezomib. Analysis of FAK promoter sequences revealed that FAK promoter harbors the NFκB and p53 binding domains. Further studies of FAK promoter activity, real-time PCR, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed that bortezomib inhibits NFκB binding on the FAK promoter, thereby reducing FAK expression. Thus, bortezomib could inhibit cancer cell growth and migration or invasion by repressing FAK expression. Since activation and overexpression of FAK has been implicated in the progression and invasion of malignant tumors, it is likely that targeting FAK with bortezomib is a potential strategy for preventing cancer metastasis. This review focuses on the molecular regulation of FAK and the potential clinical application of bortezomib.
Export Options
About this article
Cite this article as:
Ko Bor-Sheng, Chang Tzu-Ching and Liou Jun-Yang, Focal Adhesion Kinase as a Therapeutic Target of Bortezomib, Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (10) . https://dx.doi.org/10.2174/187152010794728666
DOI https://dx.doi.org/10.2174/187152010794728666 |
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
-
T Cell Tuning for Tumour Therapy: Enhancing Effector Function and Memory Potential of Therapeutic T cells
Current Gene Therapy The CLCA Gene Family A Novel Family of Putative Chloride Channels
Current Genomics Dihydroorotate Dehydrogenase Inhibitors Promote Cell Cycle Arrest and Disrupt Mitochondria Bioenergetics in Ramos Cells
Current Pharmaceutical Biotechnology Computational Approaches for Predicting Causal Missense Mutations in Cancer Genome Projects
Current Bioinformatics Histamine and Histamine Receptor Antagonists in Cancer Biology
Inflammation & Allergy - Drug Targets (Discontinued) Use of Complementary Medicine Amongst Patients on Antiretroviral Drugs in an HIV Treatment Centre in Lagos, Nigeria
Current Drug Safety Merkel Cell Carcinoma – Current State and the Future
Current Cancer Therapy Reviews Distribution, Bioactivities and Therapeutical Potentials of Pentagalloylglucopyranose
Current Bioactive Compounds In Vivo Models of Childhood Leukemia for Preclinical Drug Testing
Current Drug Targets Biochemical Markers of Renal Function
Current Medicinal Chemistry Metaboloepigenetics: The Emerging Network in Stem Cell Homeostasis Regulation
Current Stem Cell Research & Therapy Mitochondria and Organismal Longevity
Current Genomics Herpes Simplex Virus-Induced Ocular Diseases: Detrimental Interaction Between Virus and Host
Current Immunology Reviews (Discontinued) EBV-Associated Tumors: Pathogenetic Insights for Improved Disease Monitoring and Treatment
Current Cancer Therapy Reviews Meningococcal Disease and Future Drug Targets
CNS & Neurological Disorders - Drug Targets Synergistic Antiproliferative and Antiangiogenic Effects of EGFR and mTOR Inhibitors
Current Pharmaceutical Design From Natural Products to Small Molecule Ketone Histone Deacetylase Inhibitors: Development of New Class Specific Agents
Current Pharmaceutical Design Mechanisms and Immunological Roles of Apoptosis in Molluscs
Current Pharmaceutical Design IAPs, their Antagonists and their Role in Neurological Disease and Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Translational Multimodality Neuroimaging
Current Drug Targets