STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma

Naher, Lutfun; Kiyoshima, Tamotsu; Kobayashi, Ieyoshi; Wada, Hiroko; Nagata, Kazuhiro; Fujiwara, Hiroaki; Ookuma, Yukiko; Ozeki, Satoru; Nakamura, Seiji; Sakai, Hidetaka

doi:10.3892/ijo.2012.1594

Cited by 46 publications

(36 citation statements)

References 43 publications

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“…Previous findings suggested the existence of EGFRindependent STAT oncogenic properties in HNSCC, including autocrine/paracrine cytokine (IL-6, IL-10 or IL-22) stimulation or signaling through 7 nicotinic and erythropoietin receptor pathways (17,(19)(20)(21)(22)(23). Cytokine receptors are constitutively associated with members of the Janus kinase (JAK) family of protein tyrosine kinases, whereas growth factor receptors have intrinsic tyrosine kinase activity (5).…”

Section: Introductionmentioning

confidence: 99%

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

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Abstract. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway possesses confirmed oncogenic potential in oral squamous cell carcinoma (OSCC). Crosstalk with other molecular pathways contributes to STAT3 regulation in cancer. The effects of mitogen-activated protein kinases (MAPKs) and particularly extracellular signal-regulated kinase 1/2 (Erk1/2) on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examined the effects of Erk1/2 modulation on STAT3 signaling and cell growth in OSCC cells. Constitutive expression levels of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2 and cyclin D1 were assessed in OSCC cell lines. Erk1/2 modulation was achieved by pharmacological agents; siRNA silencing against Erk1/2 was also performed. Cell proliferation and viability were assessed. Erk1/2 inhibition with either U0126 treatment or specific siRNA silencing resulted in decreases in p-ser STAT3 and cyclin D1 levels and increases in p-tyr STAT3 in OSCC cells. Moreover, Erk1/2 inhibition resulted in a dose-dependent reduction in OSCC cell growth and viability. Erk1/2 induction had the opposite effects. Taken together, these results are supportive of an active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC, the significance of which requires further investigation.

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Section: Introductionmentioning

confidence: 99%

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

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“…The relative expression levels of each targeted gene were normalized using the delta-delta cycle threshold (Ct) comparative method based on the reference gene values. The specificity of the PCR products was confirmed using a melting curve and/or gel electrophoresis (Takahashi et al, 2010;Naher et al, 2012;Ookuma et al, 2013).…”

Section: Semi-quantitative Real-time Pcrmentioning

confidence: 99%

“…The protocols for organ culture were identical to those used in these studies. In order to inhibit the functions of Tb10 during tooth germ development, cultured explants were treated with siRNAs supplemented in the culture media according to the manufacturer's protocol of Lipofectamine RNAiMAX (Invitrogen) (Naher et al, 2012). siRNA for murine Tb10 (Mm_Tmsb10_0122) and a universal negative control siRNA (SigmaAldrich, St. Louis, MO, USA) were used as a target and negative control, respectively.…”

Section: Inhibition Assay For Tb10 Using Sirna On Organ Culturementioning

confidence: 99%

The expression and function of thymosin beta 10 in tooth germ development

Shiotsuka¹,

Wada²,

Kiyoshima³

et al. 2013

Int. J. Dev. Biol.

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This study presents the expression pattern and functions of thymosin beta 10 (Tb10), a Tb4 homologue during the development of mouse lower first molars. An in situ signal of Tb10 was detected on embryonic day 10.5 (E10.5)-E15.5 mainly in dental mesenchymal cells as well as in dental epithelial cells, while Tb4 was expressed in dental epithelial cells. In the late bell stage, preodontoblasts with strong Tb10 expression and preameloblasts with strong Tb4 expression exhibited face-to-face localization, suggesting that an intimate cell-cell interaction might exist between preodontoblasts and preameloblasts to form dentin and enamel matrices. A strong Tb10 signal was found in odontoblasts in the lateral side of the dental pulp and in Hertwig's epithelial root sheath, thus suggesting that Tb10 participates in the formation of the outline of the tooth root. An inhibition assay using Tb10-siRNA in E11.0 mandibles showed significant growth inhibition in the tooth germ. The Tb10-siRNA-treated E15.0 tooth germ also showed significant developmental arrest. The number of Ki67-positive cells significantly decreased in the Tb10-siRNA-treated mandibles. The cellular proliferative activity was also significantly suppressed in Tb10-siRNA-treated cultured mouse dental pulpal and epithelial cells. These results indicate that developmental arrest of the tooth germ might be caused by a reduction in cell proliferative activity. The stage-specific temporal and spatial expression pattern of Tb10 in the developing tooth germ is indicative of multiple functions of Tb10 in the developmental course from initiation to root formation of the tooth germ.

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“…Active NF-κB turns on the expression of genes that maintains cell proliferation and protects the cell from conditions that would otherwise cause it to die via apoptosis (47)(48)(49)(50). Constitutively activated STAT proteins, in particular STAT3 and STAT5, have been demonstrated to directly contribute to oncogenesis, in part, by stimulating proliferation and preventing apoptosis in various types of tumor cells (51)(52)(53). SRF is a member of the MADS box family of transcription factors.…”

Section: Comparative Proteomics Of Ron Proteins Identified In Vertebrmentioning

confidence: 99%

Integrative genomic analyses of recepteur d’origine nantais and its prognostic value in cancer

Yuan

Chu

et al. 2013

International Journal of Molecular Medicine

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Abstract. Recepteur d'origine nantais (RON) is a receptor tyrosine kinase (RTK) normally expressed at low levels in epithelial cells. RON is a 180-kDa heterodimeric protein composed of a 40-kDa α-chain and a 150-kDa transmembrane β-chain with intrinsic tyrosine kinase activity. The extracellular sequences of RON contain several domains including an N-terminal semaphorin (sema) domain, followed by the plexin, semaphorin, integrin (PSI) domain, and four immunoglobulin, plexin, transcription factor (IPT) domains. Here, we identified RON genes from 14 vertebrate genomes and found that RON exists in all types of vertebrates including fish, amphibians, birds and mammals. We found that the human RON gene showed predominant expression in the liver, lymph node, thymus, intestine, lung, mammary gland, bone marrow, brain, heart, placenta, bladder, cortex, cervix, skin, kidney and prostate. When searched in the PrognoScan database, human RON was also found to be expressed in bladder, blood, breast, glioma, esophageal, colorectal, head and neck, ovarian, lung and skin cancer. The relationship between the expression of RON and prognosis was found to vary in different cancer types, even in the same cancer from different databases. This suggests that the function of RON in these tumors may be multidimensional, not just as a tumor suppressor or oncogene. Six available single-nucleotide polymorphisms (SNPs) disrupting existing exonic splicing enhancers were identified in RON. This may contribute to the generation of active RON variants by alternative splicing, which is frequently observed in primary tumors.

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STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma

Cited by 46 publications

References 43 publications

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

The expression and function of thymosin beta 10 in tooth germ development

Integrative genomic analyses of recepteur d’origine nantais and its prognostic value in cancer

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