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J Cell Mol Med. 2020 Jan;24(2):1588-1598. doi: 10.1111/jcmm.14848. Epub 2019 Dec 2.

IL-8 promotes cell migration through regulating EMT by activating the Wnt/β-catenin pathway in ovarian cancer.

Author information

1
Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, China.
2
West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
3
West China School of Stomatology Medicine, Sichuan University, Chengdu, China.
4
Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, China.

Abstract

Interleukin-8 (IL-8), as an inflammatory chemokine, has been previously shown to contribute to tumorigenesis in several malignancies including the ovarian cancer. However, little is known about how IL-8 promotes the metastasis and invasion of ovarian cancers cells. In this study, we found that IL-8 and its receptors CXCR1 and CXCR2 were up-regulated in advanced ovarian serous cancer tissues. Furthermore, the level of IL-8 and its receptors CXCR1 and CXCR2 expression were associated with ovarian cancer stage, grade and lymph node metastasis. In vitro, IL-8 promoted ovarian cancer cell migration, initiated the epithelial-mesenchymal transition (EMT) program and activated Wnt/β-catenin signalling. However, when treated with Reparixin (inhibitor of both IL-8 receptors CXCR1 and CXCR2), effect of both endogenous and exogenous IL-8 was reversed. Together, our results indicated that IL-8 triggered ovarian cancer cells migration partly through Wnt/β-catenin pathway mediated EMT, and IL-8 may be an important molecule in the invasion and metastasis of ovarian cancer.

KEYWORDS:

Wnt/β-catenin pathway; epithelial-mesenchymal transition; interleukin-8; migration; ovarian cancer

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