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Cancers 2019, 11(3), 303; https://doi.org/10.3390/cancers11030303

Ghrelin Upregulates Oncogenic Aurora A to Promote Renal Cell Carcinoma Invasion

1
Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou 33305, Taiwan
2
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan
3
Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi Branch, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan
4
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan
5
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
*
Author to whom correspondence should be addressed.
Received: 21 January 2019 / Revised: 27 February 2019 / Accepted: 28 February 2019 / Published: 4 March 2019
(This article belongs to the Special Issue Renal Cell Carcinoma)
Full-Text   |   PDF [4102 KB, uploaded 4 March 2019]   |  

Abstract

Ghrelin is a peptide hormone, originally identified from the stomach, that functions as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and promotes growth hormone (GH) release and food intake. Increasing reports point out ghrelin’s role in cancer progression. We previously characterized ghrelin’s prognostic significance in the clear cell subtype of renal cell carcinoma (ccRCC), and its pro-metastatic ability via Snail-dependent cell migration. However, ghrelin’s activity in promoting cell invasion remains obscure. In this study, an Ingenuity Pathway Analysis (IPA)-based investigation of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset indicated the potential association of Aurora A with ghrelin in ccRCC metastasis. In addition, a significant correlation between ghrelin and Aurora A expression level in 15 ccRCC cell line was confirmed by variant probes. ccRCC patients with high ghrelin and Aurora A status were clinically associated with poor outcome. We further observed that ghrelin upregulated Aurora A at the protein and RNA levels and that ghrelin-induced ccRCC in vitro invasion and in vivo metastasis occurred in an Aurora A-dependent manner. Furthermore, MMP1, 2, 9 and 10 expressions are associated with poor outcome. In particular, MMP10 is significantly upregulated and required for the ghrelin-Aurora A axis to promote ccRCC invasion. The results of this study indicated a novel signaling mechanism in ccRCC metastasis. View Full-Text
Keywords: ghrelin; aurora A; MMP10; invasion ghrelin; aurora A; MMP10; invasion
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Lin, T.-C.; Yeh, Y.-M.; Fan, W.-L.; Chang, Y.-C.; Lin, W.-M.; Yang, T.-Y.; Hsiao, M. Ghrelin Upregulates Oncogenic Aurora A to Promote Renal Cell Carcinoma Invasion. Cancers 2019, 11, 303.

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