Noggin is associated with a poor prognosis of gastric cancer by promoting the proliferation of gastric cancer cells via the upregulation of EGFR

Sun, Zhiwei, Gao, Xiangyu, Zabkiewicz, Catherine, Ruge, Fiona, Xie, Meng, Cai, Shuo, Sun, Ping-Hui, Griffiths, Paul, Pugh, Matthew, Ji, Jiafu, Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 and Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409 2020. Noggin is associated with a poor prognosis of gastric cancer by promoting the proliferation of gastric cancer cells via the upregulation of EGFR. International Journal of Oncology 57 (3) , pp. 813-824. 10.3892/ijo.2020.5081

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Abstract

Noggin is an antagonist of bone morphogenetic proteins (BMP), being indispensable for certain developmental events. The present study aimed to examine the role of Noggin in the development and prognosis of gastric cancer (GC) and to elucidate the underlying mechanisms. The expression of Noggin in GC was evaluated by RT‑qPCR, immunohistochemistry and by the analyses of publicly available databases. The effects of Noggin on proliferation, cell cycle, adhesion, invasion, colony formation and tumour spheroid were examined following both the knockdown and overexpression of Noggin in GC cell lines. The involvement of epidermal growth factor receptor (EGFR) signalling was examined by western blot analysis and by using small molecule inhibitors. As a result, a higher expression of Noggin in GC was found to be associated with a poorer overall survival. Noggin overexpression promoted the proliferation and colony formation of GC cells by promoting cell cycle progression. The knockdown of Noggin in HGC27 cells exerted an opposite effect on proliferation, colony formation and cell cycle progression. Noggin expression positively correlated with EGFR expression in both GC cell line models and The Cancer Genome Atlas human GC cohort. Targeting EGFR and its downstream pathways diminished cell proliferation which was promoted by Noggin. Furthermore, Noggin overexpression resulted in an enhanced nuclear translocation of β‑catenin, leading to an upregulation of EGFR. Thus, the findings of the present study demonstrate that Noggin promotes the proliferation of GC cells by upregulating EGFR and enhancing a vicious circle formed by β‑catenin, EGFR, ERK and Akt.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Spandidos Publications
ISSN:	1019-6439
Funders:	China Medical Scholarship of Cardiff University and Peking University Cancer Hospital
Date of First Compliant Deposit:	16 July 2020
Date of Acceptance:	12 May 2020
Last Modified:	11 Oct 2023 19:47
URI:	https://orca.cardiff.ac.uk/id/eprint/132652

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