Androgen and fibroblast growth factor 8 (FGF8) downregulation of thrombospondin 1 (TSP1) in mouse breast cancer cells

Mattila, Mirjami; Tarkkonen, Kati; Seppänen, Jani; Ruohola, Johanna; Valve, Eeva; Härkönen, Pirkko

doi:10.1016/j.mce.2006.04.007

Cited by 15 publications

(9 citation statements)

References 48 publications

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“…Because of its antiangiogenic properties, overexpression of TSP-1 slows tumor growth in various experimental mouse models including breast cancer (Bleuel et al, 1999;Castle et al, 1997;Weinstat-Saslow et al, 1994;Volpert et al, 1998). Suppression of TSP-1 mRNA and protein in response to FGF-8b in breast cancer cells has also been shown in a previous study by our group (Mattila et al, 2006) which strengthens the finding of this study. Down regulation of genes with tumor suppressor functions such as TSP-1 and FGFR2 further supports a proliferative and tumorigenic function of FGF-8b.…”

Section: Discussionsupporting

confidence: 87%

Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

Nilsson

Brokken

Narvi

et al. 2012

Molecular and Cellular Endocrinology

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(2012). Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells. Molecular and Cellular Endocrinology, 358(1), 104-115. DOI: 10.1016/j.mce.2012.03.009 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal

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Section: Discussionsupporting

confidence: 87%

Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

Nilsson

Brokken

Narvi

et al. 2012

Molecular and Cellular Endocrinology

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“…Associations between FGFR and TSP members have been previously reported by our group and others [15,16,28,29]. The production of TSPs is associated with FGFs and determines tumor invasion and metastasis.…”

Section: Discussionsupporting

confidence: 62%

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway

Huang

Liu

Wang

et al. 2018

Cell Physiol Biochem

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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.

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“…Once activated, TGFB1 can bind to its cell membrane receptors (TGFBRI and TGFBRII), leading to phosphorylation of SMAD2 and SMAD3 proteins, which in turn complex with SMAD4, translocate to the nucleus and bind to SMAD response elements that regulate target gene expression ( Fig. 4) (Massague 2000). Like THBS1, TGFB1 expression was induced only in mature (day 11) CL, after PGF2a injection (Mondal et al 2011, Farberov & Meidan 2016.…”

Section: Thbs1-tgfb1 Axismentioning

confidence: 99%

Thrombospondin-1 at the crossroads of corpus luteum fate decisions

Farberov¹,

Basavaraja²,

Meidan³

2019

Reproduction

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The multimodular matricellular protein thrombospondin-1 (THBS1) was among the first identified endogenous antiangiogenic molecules. Recent studies have shown THBS1-mediated suppression of angiogenesis and other critical activities for corpus luteum (CL) regression. THBS1 is specifically induced by prostaglandin F2alpha in mature CL undergoing regression, whereas luteinizing signals such as luteinizing hormone and insulin reduced its expression. THBS1 interacts both synergistically and antagonistically with other essential luteal factors, such as fibroblast growth factor 2, transforming growth factor beta1 and serpin family E member 1, to promote vascular instability, apoptosis and matrix remodeling during luteal regression. Expression of THBS1 is also downregulated by pregnancy recognition signals to maintain the CL during early pregnancy. This dynamic pattern of luteal expression, the extensive interactivity with other luteal factors and strong antiangiogenic and proapoptotic activities indicate that THBS1 is a major determinant of CL fate.

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Androgen and fibroblast growth factor 8 (FGF8) downregulation of thrombospondin 1 (TSP1) in mouse breast cancer cells

Cited by 15 publications

References 48 publications

Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway

Thrombospondin-1 at the crossroads of corpus luteum fate decisions

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