Abstract
Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal blood cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in various cancers, including lymphoma and leukemia, hepatocecullar, ovarian, colorectal, breast and lung cancer. Compared to CXCR4, CXCR7 is a non-classical GPCR that is unable to activate G proteins. The function of CXCR7 is generally considered to be mediated by: (a) recruiting β-arrestin-2; (b) heterodimerizing with CXCR4; and (c) acting as a “scavenger” of CXCL12, thus lowering the level of CXCL12 to weaken the activity of CXCR4. However, the crosstalk between CXCL12/CXCR7/CXCR4 and other signaling pathways (such as the p38 MAPK pathway, the PI3K/mTOR pathway, the STAT3 signaling, and metalloproteinases MMP-9 and MMP-2) is more complicated. The function of CXCR7 is also involved in modulating tumor microenvironment, tumor cell migration and apoptosis. Understanding these complex interactions will provide insight in drug design targeting the CXCR7 as potential anticancer therapy.
Keywords: CXCL12, SDF, Migration, Apoptosis, Angiogenesis, Chemokine, Metastasis, Cancer stem cell, AMD3100, CCX771, CXCR4, CXCR7, β-arrestin, Antagonist and agonist.
Current Topics in Medicinal Chemistry
Title:Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway
Volume: 16 Issue: 13
Author(s): Dongsheng Xu, Rongshi Li, Jianguo Wu, Li Jiang and Haizhen A. Zhong
Affiliation:
Keywords: CXCL12, SDF, Migration, Apoptosis, Angiogenesis, Chemokine, Metastasis, Cancer stem cell, AMD3100, CCX771, CXCR4, CXCR7, β-arrestin, Antagonist and agonist.
Abstract: Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal blood cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in various cancers, including lymphoma and leukemia, hepatocecullar, ovarian, colorectal, breast and lung cancer. Compared to CXCR4, CXCR7 is a non-classical GPCR that is unable to activate G proteins. The function of CXCR7 is generally considered to be mediated by: (a) recruiting β-arrestin-2; (b) heterodimerizing with CXCR4; and (c) acting as a “scavenger” of CXCL12, thus lowering the level of CXCL12 to weaken the activity of CXCR4. However, the crosstalk between CXCL12/CXCR7/CXCR4 and other signaling pathways (such as the p38 MAPK pathway, the PI3K/mTOR pathway, the STAT3 signaling, and metalloproteinases MMP-9 and MMP-2) is more complicated. The function of CXCR7 is also involved in modulating tumor microenvironment, tumor cell migration and apoptosis. Understanding these complex interactions will provide insight in drug design targeting the CXCR7 as potential anticancer therapy.
Export Options
About this article
Cite this article as:
Xu Dongsheng, Li Rongshi, Wu Jianguo, Jiang Li and Zhong A. Haizhen, Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway, Current Topics in Medicinal Chemistry 2016; 16 (13) . https://dx.doi.org/10.2174/1568026615666150915120218
DOI https://dx.doi.org/10.2174/1568026615666150915120218 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Chemosensitization by Antisense Oligonucleotides Targeting MDM2
Current Cancer Drug Targets Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment
Mini-Reviews in Medicinal Chemistry Cadmium and Its Epigenetic Effects
Current Medicinal Chemistry Engagement of Renin-Angiotensin System in Prostate Cancer
Current Cancer Drug Targets Drug Targeting Approaches and Use of Drug Delivery Systems in Management of Cancer
Current Pharmaceutical Design Passive Targeting of Cyclophosphamide-Loaded Carbonate Apatite Nanoparticles to Liver Impedes Breast Tumor Growth in a Syngeneic Model
Current Pharmaceutical Design Blockade of Neoangiogenesis, a New and Promising Technique to Control the Growth of Malignant Tumors and their Metastases
Current Vascular Pharmacology Flavonoid-Based Cancer Therapy: An Updated Review
Anti-Cancer Agents in Medicinal Chemistry Gonadotropin-Releasing Hormone (GnRH) Receptors in Tumors: a New Rationale for the Therapeutical Application of GnRH Analogs in Cancer Patients?
Current Cancer Drug Targets Aminopeptidase N (APN/CD13) as a Target for Anti-Cancer Agent Design
Current Medicinal Chemistry New Perspectives in Glioma Immunotherapy
Current Pharmaceutical Design Modulation of ABC Transporters by Nuclear Receptors: Physiological, Pathological and Pharmacological Aspects
Current Medicinal Chemistry Multicolor-FISH Approaches for the Characterization of Human Chromosomes in Clinical Genetics and Tumor Cytogenetics
Current Genomics The Effects of Insulin and Insulin-Like Growth Factors on Tumor Vascularization: New Insights of Insulin-Like Growth Factor Family in Cancer
Current Medicinal Chemistry Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets Expression and Function of Organic Cation and Anion Transporters (SLC22 Family) in the CNS
Current Pharmaceutical Design Heterocyclic Scaffolds: Centrality in Anticancer Drug Development
Current Drug Targets Gonadotropin-Releasing Hormone Receptor Signaling: Biased and Unbiased
Mini-Reviews in Medicinal Chemistry Emulsomes Meet S-layer Proteins: An Emerging Targeted Drug Delivery System
Current Pharmaceutical Biotechnology An Insight into Drug Repositioning for the Development of Novel Anti-Cancer Drugs
Current Topics in Medicinal Chemistry