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
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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DOI：
10.1016/j.cellsig.2012.12.004
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发表时间：
2013-04-01
影响因子：
4.8
通讯作者：
Iizuka, Hajime
中科院分区：
文献类型：
--
作者：
Fujii, Mizue;Honma, Masaru;Iizuka, Hajime
跨膜糖蛋白podoplanin（PDPN）在细胞运动中起重要作用。然而，调节PDPN表达的机制尚未完全阐明。在这里，我们研究了细胞间接触对人鳞状细胞癌（SCC）细胞系中信号转导通路和PDPN表达的影响。PDPN表达在融合SCC细胞中高于稀疏培养物。这种PDPN诱导导致SCC细胞迁移和侵袭增加，这被shRNA PDPN敲低逆转。这种细胞密度依赖性PDPN诱导需要表皮生长因子受体（EGFR）及其效应子、信号转导子和转录激活子3（STAT 3）的激活。这些观察结果也延伸到人类临床标本，其中PDPN表达定位于原位SCC病变侵入前部的融合基底细胞层。总之，这些结果阐明了EGFR-STAT 3-PDPN通路作为靶向侵袭性SCC细胞的潜在药理学机会。(C)2012 Elsevier Inc. All rights reserved.
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. (C) 2012 Elsevier Inc. All rights reserved.