Abstract
The chemokine receptor CCR6 has been recently shown to be associated with colorectal cancer (CRC) progression. However, the direct evidence for whether CCR6 in tumors is a prognostic marker for the survival of patients with CRC and whether it plays a critical role in CRC metastasis in vivo is lacking. Here we show that the levels of CCR6 were upregulated in CRC cell lines and primary CRC clinical samples. CCR6 upregulation was closely correlated with disease stages and the survival time of CRC patients. Knockdown of CCR6 inhibited the migration of CRC cells in vitro. Overexpression of CCR6 in CRC cells increased their proliferation, migration, and colony formation in vitro and promoted their metastatic potential in vivo. CCR6 activated Akt signaling, upregulated metastasis genes and downregulated metastasis suppressor genes. Selective targeting of CCR6 in tumors dramatically inhibited the growth of CRC in mice. Thus, the tumor expression of CCR6 plays a critical role in CRC metastasis, upregulated CCR6 predicts poor survival in CRC patients, and targeting CCR6 expression in tumors may be a potential therapeutic strategy for CRC.
Highlights
Colorectal cancer (CRC) is a major health concern worldwide
It is commonly believed that during CRC metastasis, cancer cells must overcome a number of hurdles, including invasion into adjacent tissues, intravasation into blood or lymphatic vessels, survival in the circulation, extravasation from vessels at distant organs, colonization and, formation of clinically detectable metastases
The chemokine receptor CCR6 is of particular interest in CRC metastasizing to the liver [20]
Summary
Colorectal cancer (CRC) is a major health concern worldwide. Substantial progress has been made in the past decade, the challenges of treating CRC and its metastases remain formidable [1]. Chemokines are 8- to 12-kDa peptides that function as chemoattractant cytokines and exert their biological effects by interacting with G protein-linked transmembrane chemokine receptors. A number of chemokines and their corresponding receptors are known to play an important role in leukocyte trafficking and homing, especially at sites of inflammation, tissue damage and malignant cell migration [2,3]. While most chemokine receptors bind to multiple chemokines, the chemokine receptor CCR6 has only one chemokine ligand, CCL20 (previously known as macrophage inflammatory protein3a or MIP-3a) [4]
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