title: Hepatitis B virus X protein drives multiple cross-talk cascade loops involving NF-κB, 5-LOX, OPN and Capn4 to promote cell migration.
abstract: Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). However, the mechanism remains unclear. Recently, we have reported that HBx promotes hepatoma cell migration through the upregulation of calpain small subunit 1 (Capn4). In addition, several reports have revealed that osteopontin (OPN) plays important roles in tumor cell migration. In this study, we investigated the signaling pathways involving the promotion of cell migration mediated by HBx. We report that HBx stimulates several factors in a network manner to promote hepatoma cell migration. We showed that HBx was able to upregulate the expression of osteopontin (OPN) through 5-lipoxygenase (5-LOX) in HepG2-X/H7402-X (stable HBx-transfected cells) cells. Furthermore, we identified that HBx could increase the expression of 5-LOX through nuclear factor-κB (NF-κB). We also found that OPN could upregulate Capn4 through NF-κB. Interestingly, we showed that Capn4 was able to upregulate OPN through NF-κB in a positive feedback manner, suggesting that the OPN and Capn4 proteins involving cell migration affect each other in a network through NF-κB. Importantly, NF-κB plays a crucial role in the regulation of 5-LOX, OPN and Capn4. Thus, we conclude that HBx drives multiple cross-talk cascade loops involving NF-κB, 5-LOX, OPN and Capn4 to promote cell migration. This finding provides new insight into the mechanism involving the promotion of cell migration by HBx.
authors.affiliation: Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaona
authors.initials: X
authors.lastname: You
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Yumei
authors.initials: Y
authors.lastname: Du
authors.forename: Na
authors.initials: N
authors.lastname: Lv
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Changliang
authors.initials: C
authors.lastname: Shan
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002154:Calpain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D025461:Feedback, Physiological; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D053495:Osteopontin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D053495:Osteopontin; D001094:Arachidonate 5-Lipoxygenase; D008156:Luciferases; D002154:Calpain; C527669:CAPNS1 protein, human