Abstract
The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human neoplasia.
Keywords: Cancer, chromosome region maintenance 1, exportin 1, nuclear export signal, oncogene, tumor suppressor gene.
Current Cancer Drug Targets
Title:Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection
Volume: 15 Issue: 7
Author(s): Chuanwen Lu, Jose A. Figueroa, Zhongwei Liu, Venu Konala, Amardeep Aulakh, Rashmi Verma, Everardo Cobos, Maurizio Chiriva-Internati and Weimin Gao
Affiliation:
Keywords: Cancer, chromosome region maintenance 1, exportin 1, nuclear export signal, oncogene, tumor suppressor gene.
Abstract: The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human neoplasia.
Export Options
About this article
Cite this article as:
Lu Chuanwen, Figueroa A. Jose, Liu Zhongwei, Konala Venu, Aulakh Amardeep, Verma Rashmi, Cobos Everardo, Chiriva-Internati Maurizio and Gao Weimin, Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection, Current Cancer Drug Targets 2015; 15 (7) . https://dx.doi.org/10.2174/156800961507150828223554
DOI https://dx.doi.org/10.2174/156800961507150828223554 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Impact of Oncogenic Protein Tyrosine Phosphatases in Cancer
Anti-Cancer Agents in Medicinal Chemistry Effects of Tobacco Nicotine-Derived Nitrosamine Ketone (NNK) Exposures on Brain Alcohol Metabolizing Enzyme Activities
Drug Metabolism Letters Current Constructs and Targets in Clinical Development for Antibody- Based Cancer Therapy
Current Drug Targets microRNAs, Gap Junctional Intercellular Communication and Mesenchymal Stem Cells in Breast Cancer Metastasis
Current Cancer Therapy Reviews Treatment Directed to Signalling Molecules in Patients with Advanced Differentiated Thyroid Cancer
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs: Modulators of Tooth Development
MicroRNA Molecular and Cellular Regulators of Cancer Angiogenesis
Current Cancer Drug Targets Recent Highlights on Molecular Hybrids Potentially Useful in Central Nervous System Disorders
Mini-Reviews in Medicinal Chemistry Deoxypodophyllotoxin Isolated from Juniperus communis Induces Apoptosis in Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Tumor-Targeted Inhibition by a Novel Strategy - Mimoretrovirus Expressing siRNA Targeting the Pokemon Gene
Current Cancer Drug Targets Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action
Mini-Reviews in Medicinal Chemistry Modulation of Cell Death in Age-Related Diseases
Current Pharmaceutical Design Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
Current Drug Targets Carbon Nanoparticles in Mongolian Medicine Alleviate Acute Gastric Ulcer Induced by Ethanol by Regulating Fas/FasL Pathway
Current Drug Delivery Meet Our Editorial Board Member
Combinatorial Chemistry & High Throughput Screening Evolution and Pathogenesis of Oncoviruses Associated with Head and Neck Cancer: History and Current Concepts
Recent Patents on Biomarkers Human Races: Classifying People vs Understanding Diversity
Current Genomics Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets Disorders of Protein Biogenesis and Stability
Protein & Peptide Letters Structural Activity Relationship and Importance of Benzothiazole Derivatives in Medicinal Chemistry: A Comprehensive Review
Mini-Reviews in Organic Chemistry