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YWHAZ is an Invasion and Metastasis promoting genes of Lung cancer


ABSTRACT: Metastasis is a major cause leading to mortality for lung cancer patients. We identified YWHAZ as a potential metastasis-promoting candidate and found that overexpression of YWHAZ promotes lung cancer cell proliferation, anchorage-independent growth, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. It not only increases cell protrusions and branchings but also induces epithelial-mesenchymal transition. Most importantly, YWHAZ protein could prevent β-catenin from ubiquitination via its association with β-catenin and enhance slug transcriptional activity which is regulated by β-catenin/TCF signaling pathway. Moreover, YWHAZ expression was higher in tumors than in adjacent normal tissues in 63 Non-small-cell lung cancer (NSCLC) patients. NSCLC patients with high YWHAZ expressing tumors had shorter overall survival than those with low-expressing tumors. We conclude that YWHAZ play a critical role in promoting NSCLC metastasis. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. YWHAZ is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of YWHAZ in lung caner progression has not been reported, particularly in metastasis. Here, YWHAZ was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by YWHAZ-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.

ORGANISM(S): Homo sapiens

SUBMITTER: Chen CH 

PROVIDER: S-ECPF-GEOD-20318 | biostudies-other | 2012 Oct

REPOSITORIES: biostudies-other

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