Abstract
Overexpression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is a prognostic marker of many cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of NEDD9 are unclear. We found that upregulation of NEDD9 promoted migration, invasion and cell-to-extracellular matrix adhesion of HCC cells. NEDD9 also induced the epithelial-mesenchymal transition (EMT) and expression of matrix metalloprotein 2 (MMP2). Increased aldehyde dehydrogenase (ALDH) activity and CD133-positive cells were observed in HCC cells with high expression of NEDD9, corresponding to greater sphere formation in cancer stem cells (CSCs). NEDD9 deregulated Smad7 expression to inhibit Smad signaling and binding to the FAK-Src-Crk complex. We propose that this is the mechanism by which NEDD9 induced CSC properties.
Highlights
Metastasis is a key cause of poor long-term survival after surgical resection in hepatocellular carcinoma (HCC) patients, even as survival of patients with HCC improves [1]
We found that the cancer stemlike cells (CSCs) markers of aldehyde dehydrogenase (ALDH) activity and CD133 expression were significantly higher in NEDD9-overexpressing HCC cells (Figure 4B, 4C)
This study demonstrated that NEDD9 was crucial for migration and invasion of HCC cells in vitro and for metastasis in vivo
Summary
Metastasis is a key cause of poor long-term survival after surgical resection in hepatocellular carcinoma (HCC) patients, even as survival of patients with HCC improves [1]. Increasing evidence suggests that aberrant activation of the epithelial-mesenchymal transition (EMT) triggers malignant tumor progression [2]. EMT is a complex biological process characterized by the loss of epithelial markers and acquisition of mesenchymal markers that are involved in cancer metastasis [15]. Cancer cells that undergo EMT lose epithelial adhesion characteristics, detach from primary sites, and invade the lymphatic or vascular systems [3, 4]. EMT induces cells toward “stemness.” Cells with these properties are found in various cancer types. They are considered cancer stemlike cells (CSCs) [5] and are important in metastasis
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