title: NEDD9 may regulate hepatocellular carcinoma cell metastasis by promoting epithelial-mesenchymal-transition and stemness via repressing Smad7.
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.
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Diseases, Xijing Hospital, Xi'an, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Hepatobiliary Surgery, Hainan Branch of Chinese PLA general Hospital, Sanya, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Xi'an, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Tangdu Hospital, Xian, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Xi'an, China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Yue
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051906:Smad7 Protein / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D048868:Adaptor Proteins, Signal Transducing; C485285:CRK protein, human; C099942:NEDD9 protein, human; C000606023:PROM1 protein, human; D010750:Phosphoproteins; D050737:Proto-Oncogene Proteins c-crk; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D000444:Aldehyde Dehydrogenase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: cancer stem cell; developmentally downregulated 9; epithelial-mesenchymal-transition; hepatocellular carcinoma