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Updated: Aug 11, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
CXCR7 as a novel therapeutic target for advanced prostate cancer
Galina Gritsina1, Jindan Yu2,3,4
1Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abstract:
Chemokines and their cognate receptors comprise an intricate signaling network that becomes high-jacked by cancer cells for uncontrollable tumor growth and dissemination. ACKR3 (Atypical Chemokine Receptor 3), traditionally called CXCR7, is up-regulated in many cancers, including advanced prostate cancer, and represents promising targets for therapeutic intervention. Unlike typical G protein-coupled receptors such as CXCR4, CXCR7, once bound by its cognate ligand CXCL12, initiates the recruitment of β-arrestin instead of G proteins, and results in rapid internalization and degradation of CXCL12, functioning as a scavenger receptor. However, recent evidence suggests that CXCR7 may be more than a scavenger or auxiliary receptor of CXCR4 and that it may play essential roles in regulating cancer progression, some of which are independent of CXCR4 and its ligands, such as CXCL12. Constitutively active CXCR7 binds to β-arrestin. This protein complex internalizes to form a scaffold for assembling and activating various cytoplasmic kinases necessary for cell survival and tumor growth. Here we review and discuss the up-to-date knowledge on CXCR7 regulation and function and how this new understanding guides the development of CXCR7 inhibitors, focusing on prostate cancer.
Insights
Atypical Chemokine Receptor 3 (ACKR3), also known as CXCR7, is upregulated in prostate cancer and may drive tumor growth independently of its ligand CXCL12. Targeting ACKR3 offers a promising therapeutic strategy for advanced cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Chemokine receptors are crucial in cancer progression and dissemination.
- Atypical Chemokine Receptor 3 (ACKR3/CXCR7) is upregulated in various cancers, including advanced prostate cancer.
- ACKR3's role may extend beyond scavenging CXCL12, influencing cancer growth independently.
Purpose of the Study:
- To review current knowledge on ACKR3 regulation and function in cancer.
- To discuss ACKR3's emerging roles in cancer progression, including CXCR4-independent mechanisms.
- To explore how this understanding informs the development of ACKR3-targeted therapies for prostate cancer.
Main Methods:
- Literature review and synthesis of up-to-date research on ACKR3.
- Analysis of ACKR3's signaling pathways, including β-arrestin recruitment and kinase activation.
- Discussion of therapeutic strategies targeting ACKR3.
Main Results:
- ACKR3 binds β-arrestin, leading to internalization and CXCL12 degradation, acting as a scavenger.
- Constitutively active ACKR3-β-arrestin complexes form scaffolds for cytoplasmic kinases, promoting cell survival and tumor growth.
- Evidence suggests ACKR3 has crucial roles in cancer progression independent of CXCR4 and CXCL12.
Conclusions:
- ACKR3 is a significant regulator of cancer cell survival and tumor growth.
- ACKR3's CXCR4-independent functions highlight its potential as a therapeutic target.
- Targeting ACKR3 presents a promising avenue for novel prostate cancer therapies.
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