title: FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells.
abstract: To investigate the potential oncogene promoting recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT), throughput RNA sequencing was performed in a subgroup of HCC patients. The up-regulated FAM83D in HCC tissues was found and further verified in 150 patients by real-time PCR and immunohistochemistry. FAM83D overexpression significantly correlated with high HCC recurrence rate following LT and poor HCC characteristics such as high AFP, poor differentiation. Of cancer stem cells (CSCs) markers, CD44 expression was effectively suppressed when FAM83D was knocked down by siRNA. Meanwhile, the siRNA transfected cells suppressed formation of sphere and ability of self-renew. In a xenograft tumorigenesis model, FAM83D knockdown apparently inhibited tumor growth and metastasis. Microarray assays revealed that FAM83D promotes CD44 expression via activating the MAPK, TGF-β and Hippo signaling pathways. Furthermore, CD44 knockdown presented reverse effect on above signaling pathways, which suggested that FAM83D was a key activator of loop between CD44 and above signaling pathways. In conclusion, FAM83D promotes HCC recurrence by promoting CD44 expression and CD44+ CSCs malignancy. FAM83D provides a novel therapeutic approach against HCC recurrence after LT.
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors: Binyi
authors: B
authors: Lin
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors: Tianchi
authors: T
authors: Chen
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors: Qijun
authors: Q
authors: Zhang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors: Xiaoxiao
authors: X
authors: Lu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors: Zhiyun
authors: Z
authors: Zheng
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors: Jun
authors: J
authors: Ding
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors: Jinfeng
authors: J
authors: Liu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors: Zhe
authors: Z
authors: Yang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors: Lei
authors: L
authors: Geng
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors: Liming
authors: L
authors: Wu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors: Lin
authors: L
authors: Zhou
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors: Shusen
authors: S
authors: Zheng
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D000090683:Hippo Signaling Pathway; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012008:Recurrence; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D018797:Cell Cycle Proteins; C530359:FAM83D protein, human; D018960:Hyaluronan Receptors; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases
keywords: CD44; FAM83D; carcinoma stem cells; hepatocellular carcinoma; liver transplantation