title: Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial-Mesenchymal Transition Induced with TGF-β.
abstract: The epithelial-to-mesenchymal transition (EMT) is a unique process for the phenotypic changes of tumor cells characterized by a transition from polarized rigid epithelial cells to migrant mesenchymal cells, thus conferring the ability of tumor invasion and metastasis. A major challenge in the treatment of lung adenocarcinoma is to identify early stage patients at a high risk of recurrence or metastasis, thereby permitting the best therapeutic strategy and prognosis. In this study, we used a transforming growth factor-β (TGF-β)-induced EMT model to quantitatively identify protein tyrosine phosphorylation during the course of EMT in relation to malignant characteristics of lung adenocarcinoma cells. We performed relative quantitation analysis of tyrosine-phosphorylated peptides in TGF-β-treated and -untreated lung adenocarcinoma cells and identified tyrosine-phosphorylated proteins that were upregulated in TGF-β-treated cells. These include tensin-1 (TNS1) phosphorylated on Y1404, hepatocyte growth factor receptor (c-Met) phosphorylated on Y1234, and NT-3 growth factor receptor (TrkC) phosphorylated on Y516. We also found that these protein phosphorylation profiles were specifically observed in tissue samples of patients with poor prognostic lung adenocarcinoma. Tyrosine phosphorylations of these proteins represent possible candidates of prognostic prediction markers for lung adenocarcinoma.
authors.affiliation: Yokohama City University , Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Okayama
authors.affiliation: Kanagawa Cancer Center Research Institute , 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Kanagawa Cancer Center , 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Oshita
authors.affiliation: Kanagawa Cancer Center , 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Kanagawa Cancer Center , 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Yokohama City University Graduate School of Medicine , 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Yokohama City University , Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kurata
authors.affiliation: Yokohama City University , Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Yokohama City University Graduate School of Medicine , 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.affiliation: Yokohama City University , Advanced Medical Research Center, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D042241:Early Diagnosis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000032:analysis; D010766:Phosphorylation; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D016019:Survival Analysis; D000070876:Tensins; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008233:Lymphotoxin-alpha; D008840:Microfilament Proteins; D010455:Peptides; C000603369:TNS1 protein, human; D000070876:Tensins; D014443:Tyrosine; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020812:Receptor, trkC
keywords: NT-3 growth factor receptor (TrkC); epithelial-mesenchymal transition (EMT); hepatocyte growth factor receptor (c-Met); lung adenocarcinoma; prognostic prediction marker; tensin-1 (TNS1); therapeutic target; transforming growth factor-β (TGF-β); tyrosine phosphorylation