The Chemokine Receptor CXCR4 in Cell Proliferation and Tissue Regeneration

Abstract

The CXCR4 receptor upon binding its ligands triggers multiple signaling pathways that orchestrate cell migration, hematopoiesis and cell homing, and retention in the bone marrow. However, CXCR4 also directly controls cell proliferation of non-hematopoietic cells. This review focuses on recent reports pointing to its pivotal role in tissue regeneration and stem cell activation, and discusses the connection to the known role of CXCR4 in promoting tumor growth. The mechanisms may be similar in all cases, since regeneration often recapitulates developmental processes, and cancer often exploits developmental pathways. Moreover, cell migration and cell proliferation appear to be downstream of the same signaling pathways. A deeper understanding of the complex signaling originating from CXCR4 is needed to exploit the opportunities to repair damaged organs safely and effectively.

The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome

“…Within the top 100 significantly altered transcripts group, the transcript with the highest fold change in the flown neonatal versus the flown adult dataset was the chemokine CXCR4 (875.04-fold) which is a key component of cytokine–cytokine receptor interactions. CXCR4 is a regulator of cell migration and pluripotency and is highly expressed in the regenerative zebrafish model [ 20 ]. Interestingly, there is a positive correlation between CXCR4 expression and MAPK signaling [ 21 ].…”

CXCR4 Regulates Temporal Differentiation via PRC1 Complex in Organogenesis of Epithelial Glands

“…Taken together, the results of our study confirm that the epigenetic modulation by expressional regulation of PRC1 components via CXCL12/CXCR4 signaling spatiotemporally coordinates the proliferation and differentiation of developing salivary glands. Although CXCL12/CXCR4 signaling positively regulates the regeneration of multiple organs, such as the liver, lung, heart, and nervous system [ 58 ], its involvement in the context of salivary gland development has not been investigated previously. Therefore, our findings will ultimately contribute to the therapeutic approach of epithelial gland regeneration by expanding the understanding of the glandular organogenesis of epithelial organs.…”

CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment

“…CXCR4 −/− knock-out mice show a very low number of mature B and T cells in lymphoid organs and a compromised vascularization in the intestines, stomach, heart and ventricular septal defect that occurs during embryogenesis ( 19 ). CXCL12 binding to CXCR4 triggers multiple signal transduction pathways that regulate intracellular calcium flux, chemotaxis, transcription and cell survival ( 20 ). CXCL12-CXCR4 forms a complex with the Gαi subunit G protein, inhibiting the adenylyl cyclase–mediated cyclic adenosine monophosphate production and promoting mobilization of intracellular calcium.…”