The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

FGFR2 promotes gastric cancer progression by inhibiting the expression of Thrombospondin4 via PI3K-Akt-Mtor pathway

FGFR2 promotes gastric cancer progression by inhibiting the expression of Thrombospondin4 via PI3K-Akt-Mtor pathway
FGFR2 promotes gastric cancer progression by inhibiting the expression of Thrombospondin4 via PI3K-Akt-Mtor pathway

BACKGROUND/AIMS: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC.

METHODS: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model.

RESULTS: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis.

CONCLUSION: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2.

Journal Article
1015-8987
1332-1345
Huang, Tingting
047d61a7-ea98-4199-8834-25c0e0d52e6c
Liu, Dian
5a873606-ee79-47e5-9cc3-33aec13ec503
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Li, Piao
b904fd68-34f2-4071-8e80-f689f3247c44
Sun, Li
582976f8-f598-45ec-922c-df89ef1003ef
Xiong, Huihua
c835b64f-d8a2-4a72-8c53-b730db6ded56
Dai, Yuhong
e993f7ac-c007-4ed1-8864-6707fae84b90
Zou, Man
9b03dde1-d52f-4ef5-95f8-89dc325ee31c
Yuan, Xianglin
54dfb6d3-78bf-48da-936d-ded37bfcf238
Qiu, Hong
dc13a95d-9523-43de-94c3-ddd4ff9809aa
Huang, Tingting
047d61a7-ea98-4199-8834-25c0e0d52e6c
Liu, Dian
5a873606-ee79-47e5-9cc3-33aec13ec503
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e
Li, Piao
b904fd68-34f2-4071-8e80-f689f3247c44
Sun, Li
582976f8-f598-45ec-922c-df89ef1003ef
Xiong, Huihua
c835b64f-d8a2-4a72-8c53-b730db6ded56
Dai, Yuhong
e993f7ac-c007-4ed1-8864-6707fae84b90
Zou, Man
9b03dde1-d52f-4ef5-95f8-89dc325ee31c
Yuan, Xianglin
54dfb6d3-78bf-48da-936d-ded37bfcf238
Qiu, Hong
dc13a95d-9523-43de-94c3-ddd4ff9809aa

Huang, Tingting, Liu, Dian, Wang, Yihua, Li, Piao, Sun, Li, Xiong, Huihua, Dai, Yuhong, Zou, Man, Yuan, Xianglin and Qiu, Hong (2018) FGFR2 promotes gastric cancer progression by inhibiting the expression of Thrombospondin4 via PI3K-Akt-Mtor pathway. Cellular Physiology and Biochemistry, 50 (4), 1332-1345. (doi:10.1159/000494590).

Record type: Article

Abstract

BACKGROUND/AIMS: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC.

METHODS: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model.

RESULTS: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis.

CONCLUSION: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2.

Text
494590 - Version of Record
Download (2MB)

More information

Accepted/In Press date: 17 October 2018
e-pub ahead of print date: 24 October 2018
Keywords: Journal Article

Identifiers

Local EPrints ID: 425863
URI: http://eprints.soton.ac.uk/id/eprint/425863
ISSN: 1015-8987
PURE UUID: 0cd12066-cdc7-418a-83e3-b1b200d6e7ef
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

Catalogue record

Date deposited: 05 Nov 2018 17:30
Last modified: 26 Nov 2021 03:04

Export record

Altmetrics

Contributors

Author: Tingting Huang
Author: Dian Liu
Author: Yihua Wang ORCID iD
Author: Piao Li
Author: Li Sun
Author: Huihua Xiong
Author: Yuhong Dai
Author: Man Zou
Author: Xianglin Yuan
Author: Hong Qiu

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×