Dataset Information

Fibroblast Growth Factor Receptor 2 Signaling in Breast Cancer.

ABSTRACT: Fibroblast growth factor receptor 2 (FGFR2) is a membrane-spanning tyrosine kinase that mediates signaling for FGFs. Recent studies detected various point mutations of FGFR2 in multiple types of cancers, including breast cancer, lung cancer, gastric cancer, uterine cancer and ovarian cancer, yet the casual relationship between these mutations and tumorigenesis is unclear. Here we will discuss possible interactions between FGFR2 signaling and several major pathways through which the aberrantly activated FGFR2 signaling may result in breast cancer development. We will also discuss some recent developments in the discovery and application of therapies and strategies for breast cancers by inhibiting FGFR2 activities.

SUBMITTER: Lei H

PROVIDER: S-EPMC5666331 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fibroblast Growth Factor Receptor 2 Signaling in Breast Cancer.

Lei Haipeng H Deng Chu-Xia CX

International journal of biological sciences 20170905 9

Fibroblast growth factor receptor 2 (FGFR2) is a membrane-spanning tyrosine kinase that mediates signaling for FGFs. Recent studies detected various point mutations of FGFR2 in multiple types of cancers, including breast cancer, lung cancer, gastric cancer, uterine cancer and ovarian cancer, yet the casual relationship between these mutations and tumorigenesis is unclear. Here we will discuss possible interactions between FGFR2 signaling and several major pathways through which the aberrantly ac ...[more]

PMID: 29104507

Similar Datasets

Project description:INTRODUCTION:Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) facilitate breast cancer (BC) metastasis; however, stable molecular changes that result as a consequence of these processes remain poorly defined. Therefore, with the hope of targeting unique aspects of metastatic tumor outgrowth, we sought to identify molecular markers that could identify tumor cells that had completed the EMT:MET cycle. METHODS:An in vivo reporter system for epithelial cadherin (E-cad) expression was used to quantify its regulation in metastatic BC cells during primary and metastatic tumor growth. Exogenous addition of transforming growth factor ?1 (TGF-?1) was used to induce EMT in an in situ model of BC. Microarray analysis was employed to examine gene expression changes in cells chronically treated with and withdrawn from TGF-?1, thus completing one full EMT:MET cycle. Changes in fibroblast growth factor receptor type 1 (FGFR1) isoform expression were validated using PCR analyses of patient-derived tumor tissues versus matched normal tissues. FGFR1 gene expression was manipulated using short hairpin RNA depletion and cDNA rescue. Preclinical pharmacological inhibition of FGFR kinase was employed using the orally available compound BGJ-398. RESULTS:Metastatic BC cells undergo spontaneous downregulation of E-cad during primary tumor growth, and its expression subsequently returns following initiation of metastatic outgrowth. Exogenous exposure to TGF-?1 was sufficient to drive the metastasis of an otherwise in situ model of BC and was similarly associated with a depletion and return of E-cad expression during metastatic progression. BC cells treated and withdrawn from TGF-? stably upregulate a truncated FGFR1-? splice variant that lacks the outermost extracellular immunoglobulin domain. Identification of this FGFR1 splice variant was verified in metastatic human BC cell lines and patient-derived tumor samples. Expression of FGFR1-? was also dominant in a model of metastatic outgrowth where depletion of FGFR1 and pharmacologic inhibition of FGFR kinase activity both inhibited pulmonary tumor outgrowth. Highlighting the dichotomous nature of FGFR splice variants and recombinant expression of full-length FGFR1-? also blocked pulmonary tumor outgrowth. CONCLUSION:The results of our study strongly suggest that FGFR1-? is required for the pulmonary outgrowth of metastatic BC. Moreover, FGFR1 isoform expression can be used as a predictive biomarker for therapeutic application of its kinase inhibitors.

Dataset Information

Fibroblast Growth Factor Receptor 2 Signaling in Breast Cancer.

Publications

Fibroblast Growth Factor Receptor 2 Signaling in Breast Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets