title: 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.
abstract: 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.
authors.affiliation: Department of Dermatology, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Japan. ma0dj@asahikawa-med.ac.jp
authors.forename: Mizue
authors.initials: M
authors.lastname: Fujii
authors.forename: Masaru
authors.initials: M
authors.lastname: Honma
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Iizuka
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D066246:ErbB Receptors; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D016211:Transforming Growth Factor alpha; C117468:PDPN protein, human; D000098853:Podoplanin