Drug design targeting the CXCR4/CXCR7/CXCL12 pathway

Dongsheng Xu, Rongshi Li, Jianguo Wu, Li Jiang, Haizhen Andrew Zhong

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1441-1451
Number of pages11
JournalCurrent Topics in Medicinal Chemistry
Volume16
Issue number13
StatePublished - May 1 2016

Fingerprint

Drug Design
Drug Delivery Systems
Vascular Tissue Neoplasms
Neoplasms
Tumor Microenvironment
Matrix Metalloproteinase 9
p38 Mitogen-Activated Protein Kinases
Matrix Metalloproteinases
Phosphatidylinositol 3-Kinases
GTP-Binding Proteins
Ovarian Neoplasms
Cell Movement
Colorectal Neoplasms
Lymphoma
Lung Neoplasms
Blood Cells
Cell Survival
Leukemia
Cell Proliferation
Apoptosis

Keywords

  • AMD3100
  • Angiogenesis
  • Antagonist and agonist
  • Apoptosis
  • Cancer stem cell
  • CCX771
  • Chemokine
  • CXCL12
  • CXCR4
  • CXCR7
  • Metastasis
  • Migration
  • SDF
  • β-arrestin

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Drug design targeting the CXCR4/CXCR7/CXCL12 pathway. / Xu, Dongsheng; Li, Rongshi; Wu, Jianguo; Jiang, Li; Zhong, Haizhen Andrew.

In: Current Topics in Medicinal Chemistry, Vol. 16, No. 13, 01.05.2016, p. 1441-1451.

Research output: Contribution to journalArticle

Xu, Dongsheng ; Li, Rongshi ; Wu, Jianguo ; Jiang, Li ; Zhong, Haizhen Andrew. / Drug design targeting the CXCR4/CXCR7/CXCL12 pathway. In: Current Topics in Medicinal Chemistry. 2016 ; Vol. 16, No. 13. pp. 1441-1451.
@article{974d1e35513241f08c5b16847c5b664c,
title = "Drug design targeting the CXCR4/CXCR7/CXCL12 pathway",
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 = "AMD3100, Angiogenesis, Antagonist and agonist, Apoptosis, Cancer stem cell, CCX771, Chemokine, CXCL12, CXCR4, CXCR7, Metastasis, Migration, SDF, β-arrestin",
author = "Dongsheng Xu and Rongshi Li and Jianguo Wu and Li Jiang and Zhong, {Haizhen Andrew}",
year = "2016",
month = "5",
day = "1",
language = "English (US)",
volume = "16",
pages = "1441--1451",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers B.V.",
number = "13",

}

TY - JOUR

T1 - Drug design targeting the CXCR4/CXCR7/CXCL12 pathway

AU - Xu, Dongsheng

AU - Li, Rongshi

AU - Wu, Jianguo

AU - Jiang, Li

AU - Zhong, Haizhen Andrew

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - AMD3100

KW - Angiogenesis

KW - Antagonist and agonist

KW - Apoptosis

KW - Cancer stem cell

KW - CCX771

KW - Chemokine

KW - CXCL12

KW - CXCR4

KW - CXCR7

KW - Metastasis

KW - Migration

KW - SDF

KW - β-arrestin

UR - http://www.scopus.com/inward/record.url?scp=84961752949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961752949&partnerID=8YFLogxK

M3 - Article

VL - 16

SP - 1441

EP - 1451

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 13

ER -