Oncotarget

Research Papers:

An alternatively spliced variant of CXCR3 mediates the metastasis of CD133+ liver cancer cells induced by CXCL9

Qiang Ding, Yujia Xia, Shuping Ding, Panpan Lu, Liang Sun and Mei Liu _

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Oncotarget. 2016; 7:14405-14414. https://doi.org/10.18632/oncotarget.7360

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Abstract

Qiang Ding1, Yujia Xia1, Shuping Ding1, Panpan Lu1, Liang Sun2, Mei Liu1

1Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

2Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

Correspondence to:

Mei Liu, e-mail: [email protected]

Keywords: CXCR3/CXCL9, CD133+ liver cancer cells, metastasis, adhesion

Received: October 29, 2015    Accepted: January 28, 2016    Published: February 13, 2016

ABSTRACT

Metastasis of liver cancer is closely linked to tumor microenvironment, in which chemokines and their receptors act in an important role. The CXCR3, the receptor of chemokine CXCL9, belongs to a superfamily of rhodopsin-like seven transmembrane GPCRs and CXCR subfamily. In HCC tissues, CXCR3 was frequently upregulated and correlated with tumor size, tumor differentiation, portal invasion and metastasis. In the study, CXCR3-A isoform that was bound by CXCL9 was found to cause significant change of ERK1/2 phosphorylation level in the MAPK signaling pathway, consequently upregulating the MMP2 and MMP9 expression and promoting invasion and metastasis of CD133+ liver cancer cells. Also, CXCR3-A suppressed the adhesion ability of CD133+ liver cancer cells that stimulated by CXCL9 for 24h. These findings suggest that CXCR3 and its ligand CXCL9 could promote the metastasis of liver cancer cells and might be a potential target for the intervention of liver cancer metastasis.


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