Role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression.

What is it about?

Colorectal cancer (CRC) is comprised of transformed cells and non-malignant cells including cancer-associated fibroblasts (CAF), endothelial vasculature cells, and tumor-infiltrating cells. These nonmalignant cells, as well as soluble factors (e.g., cytokines), and the extracellular matrix (ECM), form the tumor microenvironment (TME). In general, the cancer cells and their surrounding TME can crosstalk by direct cell-to-cell contact and via soluble factors, such as cytokines (e.g., chemokines). TME not only promotes cancer progression through growth-promoting cytokines but also provides resistance to chemotherapy. Understanding the mechanisms of tumor growth and progression and the roles of chemokines in CRC will likely suggest new therapeutic targets. In this line, a plethora of reports has evidenced the critical role of chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis in CRC pathogenesis. In the current review, we take a glimpse into the role of the CXCR4/CXCL12 axis in CRC growth, metastasis, angiogenesis, drug resistance, and immune escape. Also, a summary of recent reports concerning targeting CXCR4/CXCL12 axis for CRC management and therapy has been delivered.

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Why is it important?

Colorectal cancer (CRC) is one of the most common causes of death in high-income countries; fatalities and occurrence are rising in low-income and developing nations as well. Early detection of CRC makes it completely treatable through surgery and subsequent therapies.CXCR4 is one of 19 well-known human chemokine receptors, which coupl Chemokines and their receptors ease the leukocyte trafficking inside the tumor tissue and implicate several aspects of tumor cell biologyes primarily by Gi proteins and is activated exclusively through binding to the chemokine CXCL12 (or SDF-1).

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