title: Ezrin expression is altered in mice lymphatic metastatic hepatocellular carcinoma and subcellular fractions upon Annexin 7 modulation in-vitro.
abstract: Ezrin and Annexin seven (A7) have been suggested to be involved in several roles in cancers metastasis. However, the role of Ezrin and the effect of A7 on Ezrin expression in lymphatic metastatic hepatocellular carcinoma (LNM-HCC) have not been extensively explored yet. This study reports expression of Ezrin in high lymphatic metastasis (Hca-F >70%) and low metastatic metastasis (Hca-P <30%) HCC cell lines, and the effect of A7 on Ezrin expression. Real-Time PCR, Western blot, Subcellular fractionation, Immunocytochemistry and Immunofluorescence were used to investigate Ezrin expression in addition to migration and invasion behaviors of A7 up-regulated Hca-F cells, A7 down-regulated Hca-P and in their respective negative control (NC) cells. Ezrin expression was higher in high LNM-HCC than low LNM-HCC (p=0.0046). Cell fractionation analysis reveals that Ezrin was highly present in the cytoplasm, nucleus and cytoskeleton of NC-Hca-F cells. However, Ezrin was highly observed in the cell membrane, nucleus and cytoskeleton of NC-Hca-P cells. A7 up-regulation in Hca-F suppressed Ezrin expression (p=0.0248), but increase the migration and invasion, whereas Ezrin was mainly located in the cytoplasm and nucleus fractions. Down-regulation of A7 in Hca-P cells, enhanced Ezrin expression (p<0.0001) in the cytoplasm and nucleus fractions, and suppressed migration and invasion. In conclusion, Ezrin may play a role in LNM-HCC and might be inversely associated with A7 expression. The subcellular localization of Ezrin and A7 was varied according to the metastatic levels. Ezrin may thus be a potential diagnostic and/or prognostic biomarker for HCC.
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Ahmed Musa
authors.initials: AM
authors.lastname: Hago
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Gamallat
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Salma Abdi
authors.initials: SA
authors.lastname: Mahmoud
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Yousra Khidir
authors.initials: YK
authors.lastname: Mahmoud
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Mohammed Ameen
authors.initials: MA
authors.lastname: Awsh
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Iddrisu Baba
authors.initials: IB
authors.lastname: Yabasin
authors.affiliation: Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Prevince, Dalian Medical University, Dalian, Liaoning 116044, China. Electronic address: jwtang_53@sina.cn.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D017310:Annexin A7 / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D051379:Mice; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D014162:Transfection; D000099149:Ezrin
chemical_list: D017310:Annexin A7; D003598:Cytoskeletal Proteins; D000099149:Ezrin; C480504:Anxa7 protein, mouse
keywords: Annexin 7; Ezrin; Hepatocellular carcinoma; Lymphatic mtastais; Subcellular fraction