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首页> 外文期刊>Cellular Signalling >Intercellular contact augments epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3)-activation which increases podoplanin-expression in order to promote squamous cell carcinoma motility
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Intercellular contact augments epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3)-activation which increases podoplanin-expression in order to promote squamous cell carcinoma motility

机译:细胞间接触可增强表皮生长因子受体(EGFR)以及信号转导和转录激活因子3(STAT3)的激活,从而增加podoplanin的表达,从而促进鳞状细胞癌的运动

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摘要

The transmembrane glycoprotein podoplanin (PDPN) plays an important role in cell motility. However, mechanisms regulating PDPN expression have not been fully elucidated. Here, we investigated the effect of intercellular contact on signal transduction pathways and PDPN expression in human squamous cell carcinoma (SCC) cell lines. PDPN expression was higher in confluent SCC cells than sparse cultures. This PDPN induction leads to increased SCC cell migration and invasion, which was reversed by shRNA PDPN knockdown. This cell density dependent PDPN induction required activation of epidermal growth factor receptor (EGFR) and its effector, signal transducer and activator of transcription 3 (STAT3). These observations also extend to human clinical specimens, in which PDPN expression localized to confluent basal cell layers at the invading front of in situ SCC lesions. Taken together, these results illuminate an EGFR-STAT3-PDPN pathway as a potential pharmacological opportunity to target invasive SCC cells.
机译:跨膜糖蛋白podoplanin(PDPN)在细胞运动中起重要作用。但是,尚未完全阐明调节PDPN表达的机制。在这里,我们调查了细胞间接触对人鳞状细胞癌(SCC)细胞系中信号转导途径和PDPN表达的影响。在融合的SCC细胞中,PDPN表达高于稀疏培养。这种PDPN诱导导致SCC细胞迁移和侵袭增加,这可通过shRNA PDPN敲低来逆转。这种依赖细胞密度的PDPN诱导需要激活表皮生长因子受体(EGFR)及其效应子,信号转导子和转录激活子3(STAT3)。这些观察结果还扩展到人类临床标本,其中PDPN表达局限于原位SCC病变侵袭前沿的汇合基底细胞层。综上所述,这些结果阐明了EGFR-STAT3-PDPN途径是靶向侵袭性SCC细胞的潜在药理学机会。

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