FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression

Stadler, Christiane; Knyazev, Pjotr; Bange, Johannes; Ullrich, Axel

doi:10.1016/j.cellsig.2005.07.002

Cited by 47 publications

(51 citation statements)

References 41 publications

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“…This suggests that FGFR4-mediated resistance to chemotherapy may not be due to increased kinase activity of the receptor. Interestingly, Gly 388 -expressing cells are less invasive compared with Arg 388 -expressing cells or cells that have no endogenous FGFR4 expression (Stadler et al 2006). This indicates that the Gly 388 allele protects patients from tumor invasion, which is consistent with a better prognosis (Bange et al 2002).…”

Section: Fgfr4supporting

confidence: 59%

“…Interference with any of these molecules could be a potential therapeutic strategy for breast cancer patients harboring the Arg 388 allele. This is supported by the observation that siRNA targeting EDG2 significantly reduces the migration of cells carrying the Arg 388 FGFR4 allele (Stadler et al 2006). In general, when targeting FGFR signaling, its role in proliferation, differentiation, migration, and angiogenesis should be kept in mind.…”

Section: Tenhagen Et Al: Fgfrs In Breast Cancermentioning

confidence: 66%

“…EDG2 induces cell migration by activation of PI3 and AKT upon binding of the LPA ligand, which is consistent with increased cell motility in cells expressing Arg 388 . The observed upregulation of MMP1 in Arg 388 -expressing cells may contribute to increased invasion due to increased degradation of the ECM (Stadler et al 2006). PAI1 has been shown to inhibit urokinase plasminogen activator (uPA) resulting in a decrease in migration and invasion.…”

Section: Tenhagen Et Al: Fgfrs In Breast Cancermentioning

confidence: 99%

“…This indicates that the Gly 388 allele protects patients from tumor invasion, which is consistent with a better prognosis (Bange et al 2002). The kinase domain was proven to be essential for this protective effect (Stadler et al 2006), suggesting that downstream signaling plays an important role. Gene expression analysis revealed…”

Section: Fgfr4mentioning

confidence: 99%

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Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets

Tenhagen¹,

Diest²,

Ivanova³

et al. 2012

Endocrine-Related Cancer

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Cancer treatments are increasingly focusing on the molecular mechanisms underlying the oncogenic processes present in tumors of individual patients. Fibroblast growth factor receptors (FGFRs) are among the many molecules that are involved in oncogenesis and are currently under investigation for their potential as drug targets in breast cancer patients. These receptor tyrosine kinases play a role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. Among breast cancer patients, several subgroups have been shown to harbor genetic aberrations in FGFRs, including amplifications of FGFR1, FGFR2, and FGFR4 and mutations in FGFR2 and FGFR4. Here, we review in vitro and in vivo models that have partly elucidated the molecular implications of these different genetic aberrations, the resulting tumor characteristics, and the potential of FGFRs as therapeutic targets for breast cancer treatment.

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Section: Fgfr4supporting

confidence: 59%

Section: Tenhagen Et Al: Fgfrs In Breast Cancermentioning

confidence: 66%

Section: Tenhagen Et Al: Fgfrs In Breast Cancermentioning

confidence: 99%

Section: Fgfr4mentioning

confidence: 99%

See 2 more Smart Citations

Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets

Tenhagen¹,

Diest²,

Ivanova³

et al. 2012

Endocrine-Related Cancer

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“…4a and 4b), indicates a functional role for the FGFR4 polymorphism in vivo in human normal lung tissue, consistent with the established in vitro functional effects of this polymorphism. 17,18 Interestingly, the gene expression profile pointed to association of the Notch biochemical pathway with Arg388 allele status, revealing upregulation of NOTCH1 and downregulation of UNC5B (Figs. 3 and 4).…”

Section: Discussionmentioning

confidence: 99%

FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung

Falvella

Frullanti

Galvan

et al. 2009

Intl Journal of Cancer

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The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) 5 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR 5 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue. ' 2009 UICC

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Lysophospholipid Signaling in Female and Male Reproductive Systems

2013

Lysophospholipid Receptors

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FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression

Cited by 47 publications

References 41 publications

Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets

Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets

FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung

Lysophospholipid Signaling in Female and Male Reproductive Systems

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