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Midkine and Hypoxia Potentiate Epithelial‐to‐Mesenchymal Transition in Human Lung Cancer Cells
Author(s) -
Zhang Hanying,
Zawada Michael,
Das Mita
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1057.1
Subject(s) - epithelial–mesenchymal transition , vimentin , stat3 , lung cancer , cancer cell , cancer research , a549 cell , stat protein , microbiology and biotechnology , tumor microenvironment , mesenchymal stem cell , biology , pathology , hypoxia (environmental) , chemistry , cancer , phosphorylation , metastasis , medicine , immunohistochemistry , genetics , organic chemistry , tumor cells , oxygen
Epithelial‐to‐mesenchymal transition (EMT) plays an important role during progression of lung cancer. Recently, hypoxia and midkine (MK) have been shown to be key regulators of EMT in various types of cancer cells. Signal transducer and activator of transcription 3 (STAT3) also plays a critical role in this process. Therefore, we hypothesize that MK will enhance EMT in lung cancer cells grown in a hypoxic microenvironment through STAT3 activation. Human lung cancer cells (A549) were exposed to 1% oxygen in the presence of MK to test our hypothesis. EMT was evaluated by assessment of cell morphology as well as expression of marker proteins. Cell morphology was altered from cuboidal to elongated shape after 48 hours of treatments. Levels of E‐cadherin, marker of epithelial cells, were decreased. However, expression of alpha smooth muscle actin (αSMA) and vimentin, markers of mesenchymal cells, were augmented. Hypoxia/MK treatment stimulated STAT3 phosphorylation at Ser727 as well as Tyr705 residues. Interestingly, the two phosphospecies had unique subcellular localization patterns. PhophoSTAT3(Tyr705) was restricted to focal points within the cytoplasm, whereas Ser727 phosphoSTAT3 was present predominantly in the nuclear compartment. Therefore, our data strongly suggest that hypoxia/MK potentiates EMT process and this process might be mediated through STAT3 activation in human lung cancer cells. Funded by HL64917 (MD); P20RR016474 (NCRR & Wyoming INBRE)