These findings demonstrate the first evidence for epigenetic regulation of CXCR4 in human cancers, providing new insights into the role of CXCR4/CXCL12 interactions in tumor progression.
The CXCL12/CXCR4 pathway, which is involved in biological phenomena such as inflammation, lymphoid homing and regeneration, may play an important role in tumor progression and distant metastasis, especially in organ-selective metastasis.
Focusing on a specific subset of genes, we found that the ability of stromal ATF3 to promote cancer progression is mediated by transcriptional repression of CLDN1 and induction of CXCL12 and RGS4.
Signals mediated by CXCL12 (SDF1) and its receptor CXCR4 are centrally involved in cancer progression, both directly by activating cancer cells and indirectly by inducing angiogenesis plus recruiting T regulatory and plasmacytoid dendritic immune cells.
To investigate CXCL12-CXCR4 signaling in ovarian cancer and establish effects of inhibiting this pathway on tumor progression and survival, we designed a Gaussia luciferase complementation imaging reporter system to detect CXCL12 binding to CXCR4 in ovarian cancer cells.
Mechanisms that regulate availability of CXCL12 in tumor microenvironments will substantially impact cancer progression and ongoing efforts to target the CXCL12-CXCR4 pathway for cancer chemotherapy.
The stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis and Wingless and INT-1 (Wnt)/β-catenin pathway has been related to cancer progression.
As the bone marrow constitutes a unique microenvironment for cancer cells, the CXCL12-CXCR4 axis assists the bone marrow in regulating cancer progression.
The chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 (SDF-1) plays an important role in tumor progression and are associated with angiogenesis.
We also demonstrated that restored expression of CXCL12 dampened miR-448-mediated suppression of tumor progression, which suggests the important role of miR-448 in tumor progression.
Recent studies suggest that SDF-1 and CXCR4 are expressed in certain cancer cells, and malignant cells use this chemokine/receptor system to promote tumor progression and metastasis.
The chemokine CXCL12 (also termed SDF-1, stromal cell-derived factor-1) and its receptors CXCR4 and CXCR7 are known to play a pivotal role in tumor progression including glioblastomas (GBM).