Research Papers:

Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways

Yeo Song Lee _, So-Young Kim, Su Jeong Song, Hye Kyung Hong, Yura Lee, Bo Young Oh, Woo Yong Lee and Yong Beom Cho

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Oncotarget. 2016; 7:36842-36853. https://doi.org/10.18632/oncotarget.9209

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Yeo Song Lee1,*, So-Young Kim1,*, Su Jeong Song1, Hye Kyung Hong1, Yura Lee1, Bo Young Oh2, Woo Yong Lee2,3, Yong Beom Cho2,3,4

1Samsung Biomedical Research Institute, Sungkyunkwan University, Seoul, Republic of Korea

2Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

3Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea

4Department of Medical Device Management & Research, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Yong Beom Cho, e-mail: [email protected]

Keywords: CCL7, CCR3, ERK-JNK signaling, metastasis, colon cancer

Received: August 24, 2015    Accepted: April 22, 2016    Published: May 6, 2016


Chemokine ligand 7 (CCL7) enhances cancer progression and metastasis via epithelial-mesenchymal transition (EMT). However, little is known about the molecular mechanism of CCL7-induced EMT signaling cascade in colon cancer. Thus, the objective of this study was to investigate CCL7-induced EMT signaling pathway and its role in the progression and metastasis of colon cancer. To demonstrate the effect of CCL7 on EMT induction, HCT116 and HT29 cells overexpressing CCL7 were generated. CCL7-induced EMT and its downstream signaling pathway were evaluated by both in vitro and in vivo experiments. In in vitro studies, CCL7 was found to interplay with CC chemokine receptor 3 (CCR3), resulting in enhanced cellular proliferation, invasion, and migration via ERK and JNK signaling pathway. To validate these findings, we established ectopic and orthotopic mouse models injected with CCL7-overexpressed cells. In ectopic mouse models, we observed that CCL7-overexpressed cells grew significantly faster than control cells. In orthotopic mouse models, we found that liver and lung metastasis developed only in mice injected with CCL7-overexpressed cells. This study is the first one focusing on the EMT cascade via CCL7-CCR3-ERK-JNK signaling axis in colon cancer. Our novel findings will improve our understanding on the mechanism of metastatic process and provide potential therapeutic strategies for preventing metastasis in colon cancer.

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