Top

Journal of Cancer Research and Clinical Oncology

Published in:

Open Access 01-01-2018 | Original Article – Cancer Research

Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade

Authors: Akihiro Asai, Yasuyoshi Miyata, Kosuke Takehara, Shigeru Kanda, Shin-ichi Watanabe, Peter A. Greer, Hideki Sakai

Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2018

Abstract

Purpose

The feline sarcoma oncogene protein (FES) is a non-receptor tyrosine kinase implicated in both oncogenesis and tumor suppression. Here, cancer cell lines and human tissues were employed to clarify the pathological and prognostic significance of FES in bladder cancer.

Methods

The relationship between FES expression and cancer aggressiveness was investigated using 3 cell lines (T24: corresponding to grade 3, 5637: corresponding to grade 2, and RT4: corresponding to grade 1) and 203 tissues derived from human bladder malignancies. Proliferation, invasion, and migration of cancer cells were assessed following the knockdown (KD) of FES expression by the siRNA method. Relationships between FES expression and pathological features, aggressiveness, and outcome were investigated.

Results

FES-KD inhibited the proliferation, migration, and invasion of T24 cells but not of RT4 cells and 5637 cells. Considering all patients, FES expression demonstrated a negative relationship with grade but no association with muscle invasion or cancer cell proliferation. However, it was positively correlated with pT stage and cell proliferation in high-grade tumors (p = 0.002); no such association was found for low-grade tumors. In addition, elevated FES expression was a negative prognostic indicator of metastasis after radical surgery for patients with high-grade tumors (p = 0.021) but not for those with low-grade malignancies.

Conclusions

FES appeared to act as a suppressor of carcinogenesis, being associated with low tumor grade in the overall patient group. However, its expression correlated with cancer aggressiveness and poor outcome in high-grade bladder cancer. FES, therefore, represents a potential therapeutic target and useful prognostic factor for such patients.

Abufaraj M et al (2016) Management of muscle invasive, locally advanced and metastatic urothelial carcinoma of the bladder: a literature review with emphasis on the role of surgery. Transl Androl Urol 5:735–744CrossRefPubMedPubMedCentral

Bardelli A et al (2003) Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300:949CrossRefPubMed

Bryan RT et al (2010) Cadherin switching and bladder cancer. J Urol 184:423–431. doi:10.1016/j.juro.2010.04.016 CrossRefPubMed

Delfino FJ et al (2006) A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal cancer. J Biol Chem 281:8829–8835CrossRefPubMed

Elsamman E et al (2006) Differences in gene expression between noninvasive and invasive transitional cell carcinoma of the human bladder using complementary deoxyribonucleic acid microarray: preliminary results. Urol Oncol 24:109–115CrossRefPubMed

Erickson DR et al (2008) Differentiation associated changes in gene expression profiles of interstitial cystitis and control urothelial cells. J Urol 180:2681–2687. doi:10.1016/j.juro.2008.08.007 CrossRefPubMed

Greer P (2002) Closing in on the biological functions of Fps/Fes and Fer. Nat Rev Mol Cell Biol 3:278–289CrossRefPubMed

Hu J et al (2017) MicroRNA-125b inhibits AML cells differentiation by directly targeting FES. Gene 620:1–9. doi:10.1016/j.gene.2017.04.002 CrossRefPubMed

Izuhara K et al (1996) Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase. Blood 88:3910–3918PubMed

Kanda S et al (2009) Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells. Int J Oncol 34:89–96PubMedPubMedCentral

Leick MB et al (2017) The future of targeting FLT3 activation in AML. Curr Hematol Malig Rep 12:153–167. doi:10.1007/s11899-017-0381-2 CrossRefPubMed

Luo Y et al (2017) Elevated microRNA-125b levels predict a worse prognosis in HER2-positive breast cancer patients. Oncol Lett 13:867–874. doi:10.3892/ol.2016.5482 PubMed

Mialhe A et al (1997) Expression of E-cadherin and alpha-, beta- and gamma-catenins in human bladder carcinomas: are they good prognostic factors? Invasion Metastasis 17:124–137PubMed

Mitsunari K et al (2016) Human antigen R is positively associated with malignant aggressiveness via upregulation of cell proliferation, migration, and vascular endothelial growth factors and cyclooxygenase-2 in prostate cancer. Transl Res 175:11–128. doi:10.1016/j.trsl.2016.04.002 CrossRef

Miyata Y et al (2012) Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer. Prostate 72:201–208. doi:10.1002/pros.21422 CrossRefPubMed

Miyata Y et al (2014) Heme oxygenase-1 expression is associated with tumor aggressiveness and outcomes in patients with bladder cancer: a correlation with smoking intensity. Transl Res 164:468–476. doi:10.1016/j.trsl.2014.06.010 CrossRefPubMed

Naba A et al (2008) Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering. EMBO J 27:38–50CrossRefPubMed

Ohba K et al (2011) Clinical significance and predictive value of prostaglandin E2 receptors (EPR) 1–4 in patients with renal cell carcinoma. Anticancer Res 31:597–605PubMed

Olvedy M et al (2017) Comparative oncogenomics identifies tyrosine kinase FES as a tumor suppressor in melanoma. J Clin Investig 127:2310–2325. doi:10.1172/JCI91291 CrossRefPubMedPubMedCentral

Parsons SA et al (2006) The Fps/Fes kinase regulates the inflammatory response to endotoxin through down-regulation of TLR4, NF-kappaB activation, and TNF-alpha secretion in macrophages. J Leukoc Biol 80:1522–1528CrossRefPubMed

Parsons SA et al (2007) The Fps/Fes kinase regulates leucocyte recruitment and extravasation during inflammation. Immunology 122:542–550CrossRefPubMedPubMedCentral

Sangrar W et al (2005) An identity crisis for Fps/Fes: oncogene or tumor suppressor? Cancer Res 65:3322–3518CrossRef

Smith JA (2010) Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and beta1 integrin receptors. Cell Signal 22:427–436. doi:10.1016/j.cellsig.2009.10.014 CrossRefPubMed

Truesdell PF et al (2009) Fps/Fes knockout mice display a lactation defect and the fps/fes tyrosine kinase is a component of E-cadherin-based adherens junctions in breast epithelial cells during lactation. Exp Cell Res 315:2929–2940. doi:10.1016/j.yexcr.2009.08.021 CrossRefPubMed

Voisset E et al (2010) FES kinases are required for oncogenic FLT3 signaling. Leukemia 2:721–728. doi:10.1038/leu.2009.301 CrossRef

Weir MC et al (2017) Dual inhibition of FES and Flt3 tyrosine kinases potently inhibits Flt3-ITD + AML cell growth. PLoS One 12:e0181178. doi:10.1371/journal.pone.0181178.eCollection CrossRefPubMedPubMedCentral

Xu G et al (2004) Continuous association of cadherin with beta-catenin requires the non-receptor tyrosine-kinase Fer. J Cell Sci 117:3207–3219CrossRefPubMed

Zhang S et al (2011) Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis and infiltrating macrophages. Cancer Res 71:1465–1473. doi:10.1158/0008-5472 CrossRefPubMed

Zoubeidi A et al (2009) The fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth. Mol Cancer Res 7:142–155. doi:10.1158/1541-7786 CrossRefPubMed

Title: Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade
Authors: Akihiro Asai
Yasuyoshi Miyata
Kosuke Takehara
Shigeru Kanda
Shin-ichi Watanabe
Peter A. Greer
Hideki Sakai
Publication date: 01-01-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 1/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2524-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Differences in the prognosis of HPV16-positive patients with squamous cell carcinoma of head and neck according to viral load and expression of P16

Qualitative evaluation of mobile cancer apps with particular attention to the target group, content, and advertising

Prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell carcinomas of the head and neck

Can checkpoint inhibitor therapy improve response to chemotherapy?

The usefulness of testosterone administration in identifying false-positive elevation of serum human chorionic gonadotropin in patients with germ cell tumor

Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page