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Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial–Mesenchymal Transition Induced with TGF-β

Authors: Akiko, Okayama; Yohei, Miyagi; Fumihiro, Oshita; Hiroyuki, Ito; Haruhiko, Nakayama; Mayuko, Nishi; Yoichi, Kurata; +3 Authors

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.

Keywords

Adult, Aged, 80 and over, Male, Epithelial-Mesenchymal Transition, Lung Neoplasms, Microfilament Proteins, Adenocarcinoma of Lung, Epithelial Cells, Adenocarcinoma, Middle Aged, Gene Expression Regulation, Neoplastic, Early Diagnosis, Cell Line, Tumor, Humans, Female, Phosphorylation, Peptides, Lymphotoxin-alpha, Aged, Neoplasm Staging

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
19
Top 10%
Average
Top 10%