title: Podoplanin promotes cell migration via the EGF-Src-Cas pathway in oral squamous cell carcinoma cell lines.
abstract: Human podoplanin is a type-1 transmembrane sialomucin-like glycoprotein that is involved in cell migration, tumor cell invasion and metastasis. Our recent study of oral squamous cell carcinoma (OSCC) demonstrated that the degree of immunohistochemical expression of podoplanin was correlated with the severity of epithelial dysplasia and significantly associated with a poor pathologic grade of differentiation. Furthermore, it has been reported that Src directly associates with the epidermal growth factor receptor (EGFR) in OSCC cells upon stimulation with EGF and phosphorylates Crk-associated substrate (Cas), podoplanin acting downstream of Src and Cas to promote cell migration. However, the molecular function of podoplanin remains unclear. In this study we performed real-time RT-PCR, Western blotting and scratch assay using OSCC cell lines in order to clarify the molecular biological function of podoplanin expression associated with various growth factors including EGF and with the Src-Cas signaling pathway. Podoplanin was found to have a marked influence on cancer cell migration and the expression of matrix metalloprotease-9 (MMP-9) in the oral cavity upon stimulation with EGF. Podoplanin promotes oral cancer cell migration, and the EGF-Src-Cas pathway is one of the possible mechanisms responsible for progression of cancer in the oral cavity.
authors.affiliation: Division of Pathology, Department of Diagnostic & Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan. harumi-i@dent.meikai.ac.jp
authors.forename: Harumi
authors.initials: H
authors.lastname: Inoue
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Fumio
authors.initials: F
authors.lastname: Ide
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohmori
authors.forename: Akihito
authors.initials: A
authors.lastname: Tomomura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sakashita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kusama
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D050719:Crk-Associated Substrate Protein; D004815:Epidermal Growth Factor / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000494:pharmacology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059016:Tumor Microenvironment; D000098853:Podoplanin
chemical_list: D050719:Crk-Associated Substrate Protein; D004815:Epidermal Growth Factor; D020780:Matrix Metalloproteinase 9; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C117468:PDPN protein, human; D000098853:Podoplanin