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

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.