Page 47 - @林口醫研部201912電子報

‣研究背景

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.

‣應⽤性

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 (Figure 1). 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.

Department of Medical Research & Development, Linkou Newsletter 47