title: EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression.
abstract: Ebp1, a protein identified by its interactions with the ErbB3 receptor, has been characterized as a negative regulator of cancers. RAS GTPase-activating protein (RasGAP), RASAL1, was recently identified as a major tumor suppressor in thyroid cancer. In this study, we examined EBP1 expression in papillary and follicular thyroid cancer cells. We found that compared with normal thyroid cells, TPC1, WRO, and FTC133 thyroid tumor cells exhibited lower EBP1 expression at messenger RNA (mRNA) and protein levels. We then investigated the effects of forced EBP1 expression on growth, migration, and invasiveness of thyroid tumor cells. By using MTT and Boyden chamber assays, we showed that EBP1 overexpression dramatically reduced growth rate, migration, and invasiveness of K1 and FTC133 thyroid tumor cells. Furthermore, we explored the molecular mechanism underlying the effects of EBP1 on the cells by disclosing the correlation of EBP1 and RASAL1 expression. RASAL expression was elevated in thyroid tumor cells overexpressing EBP1. Knockdown RASAL by transduction of RASAL1 shRNA lentiviral particles markedly reduced RASAL levels with restoration of EBP1, and RASAL1 knockdown abrogated the effects of forced EBP1 expression on cell growth, migration, and invasiveness of thyroid tumor cells. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong, 276003, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong, 276003, People's Republic of China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong, 276003, People's Republic of China.
authors.forename: Liujuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory Medicine, Linyi People's Hospital, Linyi, Shandong, 276003, People's Republic of China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Surgery, People's Hospital of Linzi District Affiliated to Binzhou Medical College, Zibo, Shandong, 255400, People's Republic of China. zhijunzhang58@yahoo.com.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020690:GTPase-Activating Proteins; C101633:PA2G4 protein, human; C580923:RASAL1 protein, human; D016601:RNA-Binding Proteins
keywords: EBP1; Invasiveness; Migration; RASAL1; Thyroid cancer