title: Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma.
abstract: OBJECTIVE
  Trophoblast cell surface antigen 2 (TROP2) or tumor-associated calcium signal transducer 2 (TACSTD2) is a 36-kDa type I transmembrane glycoprotein and exerts dual functions as an oncogene and tumor suppressor in cancer cells. In this study, we investigated the expression and functions of TROP2 in liver fluke-associated cholangiocarcinoma (CCA).
  
  
  METHODS
  TROP2 expression in 85 CCA tissues was detected by using immunohistochemistry. The methylation status of TROP2 promoter was studied in 15 matched pairs of normal and CCA formalin fixed paraffin embedded (FFPE) tissues using the bisulfite genomic sequencing (BGS) method. The functions of TROP2 on cancer cell behavior were investigated using siRNA in CCA cell lines. Proliferation, migration and invasion assays were performed. A PCR array was used to evaluate the impact of TROP2 knockdown on the gene expression profiles.
  
  
  RESULTS
  TROP2 was highly expressed in all normal bile duct epithelia, but significantly down-regulated in CCA cells. Sixty percent of CCA revealed promoter hypermethylation compared to the corresponding adjacent normal tissues. TROP2 knockdown significantly enhanced the proliferation and migration in CCA cell lines, and altered the expressions of MARCK, EMP1 and FILIP1L.
  
  
  CONCLUSIONS
  We provide new evidence that TROP2 is epigenetically down-regulated and operates as a negative regulator of cell proliferation and migration in liver fluke-associated CCA.
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Kanlayanee
authors.initials: K
authors.lastname: Sawanyawisuth
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Nattawat
authors.initials: N
authors.lastname: Tantapotinan
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.affiliation: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ratthaphol
authors.initials: R
authors.lastname: Kraiklang
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Anucha
authors.initials: A
authors.lastname: Puapairoj
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005210:Fasciola hepatica / Q000302:isolation & purification*; D005211:Fascioliasis / Q000150:complications / Q000469:parasitology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C504459:FILIP1L protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; C499380:TACSTD2 protein, human; C097051:epithelial membrane protein-1; D000076250:Myristoylated Alanine-Rich C Kinase Substrate