Abstract
The two members of the LIM domain kinase family (LIMK1 and LIMK2) represent crucial keys in the signaling pathways that modulate the structure and activity of actin cytoskeleton. They maintain the optimal balance between phosphorylated and unphosphorylated cofilin that in turn acts by severing filamentous actin into globular actin and ensures actin turnover and cytoskeleton regulation. Many macromolecular partners able to regulate LIMK activity (positive and negative regulators) do exist. Proteins that enhance or reduce the nucleocytoplasmic shuttling of LIMK by direct or indirect interaction are also known. Among many LIMK activators, members of the Rho family of small GTPases (i.e., Rho, Rac, and Cdc42) and their downstream effectors (i.e., ROCK, PAK, and MK2) are involved in the progression of various human cancers toward invasive and metastatic stages. As LIMK are centrally positioned in the pathways leading to cytoskeleton dynamics and regulation, they could be considered as valuable targets for actin regulation. Fine modulation of LIMK activity could be a major challenge to inhibit tumor cell invasion mediated by one or a combination of the upstream signaling factors. As LIMK play a critical role in tumor cell invasion, they may be candidate targets for developing novel therapeutic agents toward tumor invasion and metastasis.
Keywords: Actin cytoskeletal dynamics, actin-depolymerizing factor, cofilin, cancer cells, LIM domain kinases, metastasis, small molecule LIMK inhibitors
Current Cancer Drug Targets
Title:Recent Findings Confirm LIM Domain Kinases as Emerging Target Candidates for Cancer Therapy
Volume: 12 Issue: 5
Author(s): F. Manetti
Affiliation:
Keywords: Actin cytoskeletal dynamics, actin-depolymerizing factor, cofilin, cancer cells, LIM domain kinases, metastasis, small molecule LIMK inhibitors
Abstract: The two members of the LIM domain kinase family (LIMK1 and LIMK2) represent crucial keys in the signaling pathways that modulate the structure and activity of actin cytoskeleton. They maintain the optimal balance between phosphorylated and unphosphorylated cofilin that in turn acts by severing filamentous actin into globular actin and ensures actin turnover and cytoskeleton regulation. Many macromolecular partners able to regulate LIMK activity (positive and negative regulators) do exist. Proteins that enhance or reduce the nucleocytoplasmic shuttling of LIMK by direct or indirect interaction are also known. Among many LIMK activators, members of the Rho family of small GTPases (i.e., Rho, Rac, and Cdc42) and their downstream effectors (i.e., ROCK, PAK, and MK2) are involved in the progression of various human cancers toward invasive and metastatic stages. As LIMK are centrally positioned in the pathways leading to cytoskeleton dynamics and regulation, they could be considered as valuable targets for actin regulation. Fine modulation of LIMK activity could be a major challenge to inhibit tumor cell invasion mediated by one or a combination of the upstream signaling factors. As LIMK play a critical role in tumor cell invasion, they may be candidate targets for developing novel therapeutic agents toward tumor invasion and metastasis.
Export Options
About this article
Cite this article as:
Manetti F., Recent Findings Confirm LIM Domain Kinases as Emerging Target Candidates for Cancer Therapy, Current Cancer Drug Targets 2012; 12 (5) . https://dx.doi.org/10.2174/156800912800673266
DOI https://dx.doi.org/10.2174/156800912800673266 |
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
-
BRAF Status in Papillary Microcarcinomas of the Thyroid Gland: a Brief Review
Current Molecular Medicine Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK Signaling
Current Cancer Drug Targets In Vitro Evaluation of Chloroaluminum Phthalocyanine Nanoemulsion and Low-Level Laser Therapy on Human Skin Dermal Equivalents and Bone Marrow Mesenchymal Stem Cells
Current Medicinal Chemistry Data Visualization and Feature Selection Methods in Gel-based Proteomics
Current Protein & Peptide Science Organic Toxins as Tools to Understand Ion Channel Mechanisms and Structure
Current Topics in Medicinal Chemistry Editorial:[Special Issue: Post-Translational Proteomics and its Application (Guest Editor: Qing-Yu He)]
Current Proteomics Targeting Cancer and Neuropathy with Histone Deacetylase Inhibitors:Two Birds with One Stone?
Current Cancer Drug Targets Systems Biology Approaches to Pancreatic Cancer Detection, Prevention and Treatment
Current Pharmaceutical Design ABC Multidrug Transporters: Target for Modulation of Drug Pharmacokinetics and Drug-Drug Interactions
Current Drug Targets pH-Sensitive PEGylated Liposomes Functionalized With a Fibronectin-Mimetic Peptide Show Enhanced Intracellular Delivery to Colon Cancer Cells
Current Pharmaceutical Biotechnology The Current WHO Classification of Tumours of the Central Nervous System: Histopathology and Additional Diagnostic Methods
Current Medical Imaging 5' Adenosine Monophosphate-Activated Protein Kinase Modulators as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design Functional Proteomics Using Direct Protein Inactivation
Current Proteomics Construction, Expression and Functional Characterization of the β-Lactamase with αv Integrin Ligands
Protein & Peptide Letters Extracellular HSP90: An Emerging Target for Cancer Therapy
Current Signal Transduction Therapy P-Glycoprotein - Implications of Metabolism of Neoplastic Cells and Cancer Therapy
Current Cancer Drug Targets Molecular Determinants of Fluoroquinolone Antibacterial Agents Pharmacokinetics
Current Clinical Pharmacology Vascular Endothelial Growth Factor Receptor as Target for Advanced Non-Small Cell Lung Cancer Therapy
Current Drug Targets Docosahexaenoic Acid (DHA) Sensitizes Brain Tumor Cells to Etoposide-Induced Apoptosis
Current Molecular Medicine