The function of SARI in modulating epithelial-mesenchymal transition and lung adenocarcinoma metastasis

• Published in: PloS one 2012-09, Vol.7 (9), p.e38046
• Main Authors: Wang, Changli, Su, Yanjun, Zhang, Lianmin, Wang, Meng, You, Jian, Zhao, Xiaoliang, Zhang, Zhenfa, Liu, Jun, Hao, Xishan
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Animals; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Biology; Biomarkers; Cadherins - genetics; Cadherins - metabolism; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Development and progression; Diagnosis; E-cadherin; Epithelial-Mesenchymal Transition - genetics; Extracellular matrix; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Health aspects; Health risks; Humans; Interferon; Kinases; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lungs; Lymph nodes; Lymphatic Metastasis; Male; Medicine; Mesenchyme; Metastases; Metastasis; Mice; Mice, Nude; Microscopy; Middle Aged; Morphology; Motility; Neoplasm Transplantation; Phosphorylation; Radiotherapy; Signal Transduction; Signaling; Stem cells; Transcription factors; Tumor cell lines; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Vimentin; Vimentin - genetics; Vimentin - metabolism; Xenografts; β-catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038046

The SARI (suppressor of AP-1, regulated by IFN) gene, which is also called BATF2, is associated with the risk of several kinds of cancer, and loss of SARI expression is frequently detected in aggressive and metastatic cancer. However, the functional role of SARI in lung adenocarcinoma remains unknown. We have shown that loss of SARI expression initiates epithelial-mesenchymal transition (EMT), which is visualized by repression of E-cadherin and up-regulation of vimentin in lung adenocarcinoma cell lines and in clinical lung adenocarcinoma specimens. Using a human lung xenograft-mouse model, we observed that knocking down endogenous SARI in human carcinoma cells leads to the development of multiple lymph node metastases. Moreover, we showed that SARI functions as a critical protein in regulating EMT by modulating the (GSK)-3β-β-catenin signaling pathway. These results demonstrate the mechanism of SARI function in EMT and suggest that assessment of SARI may serve as a prognostic biomarker and potential therapeutic target for lung adenocarcinoma metastasis.