Abstract
Metastasis is a predominant cause of cancer death and the major challenge in treating lung adenocarcinoma (LADC). Therefore, exploring new metastasis-related genes and their action mechanisms may provide new insights for developing a new combative approach to treat lung cancer. Previously, our research team discovered that the expression of the inhibitor of DNA binding 4 (Id4) was inversely related to cell invasiveness in LADC cells by cDNA microarray screening. However, the functional role of Id4 and its mechanism of action in lung cancer metastasis remain unclear. In this study, we report that the expression of Id4 could attenuate cell migration and invasion in vitro and cancer metastasis in vivo. Detailed analyses indicated that Id4 could promote E-cadherin expression through the binding of Slug, cause the occurrence of mesenchymal-epithelial transition (MET), and inhibit cancer metastasis. Moreover, the examination of the gene expression database (GSE31210) also revealed that high-level expression of Id4/E-cadherin and low-level expression of Slug were associated with a better clinical outcome in LADC patients. In summary, Id4 may act as a metastatic suppressor, which could not only be used as an independent predictor but also serve as a potential therapeutic for LADC treatment.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide [1,2]
inhibitor of DNA binding 4 (Id4) Expression Inversely Correlates with Lung Cancer Cell Invasiveness
Id4 Affects the Malignancy of Cancer Cell through the Regulation of Epithelial–Mesenchymal Transition expressing lung cancer cells was first examined in detail, and we found that the CL1-0/Id4-silencing
Summary
Lung cancer is the leading cause of cancer-related death worldwide [1,2]. Cancers 2019, 11, 2021 general, lung cancer can be divided into two major groups called non-small cell lung cancer (NSCLC). The former accounts for 85% of lung cancer patients and close to 50% of this proportion are lung adenocarcinoma (LADC) patients. Despite advances in LADC treatment that have been made over the past decades, the molecular mechanism of this type of cancer has remained unclear [3]. Identifying novel genes and their mechanisms of action involved in LADC progression and metastasis may provide new insights into the pathogenesis and management of lung cancer treatment
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