title: ZKSCAN3 Facilitates Liver Metastasis of Colorectal Cancer Associated with CEA-expressing Tumor.
abstract: OBJECTIVE
  Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) is overexpressed in invasive colorectal cancer (CRC) cells and regulates the expression of several genes favoring tumor progression, including vascular endothelial growth factor (VEGF) and integrin β4. We evaluated the association of ZKSCAN3 and colorectal cancer liver metastasis (CLM) to determine whether it is related to invasive signaling pathways.
  
  
  METHODS
  The ratios of expression by primary tumor to normal tissue and metastatic tumor to normal tissue were compared between ZKSCAN3-overexpressing and underexpressing primary tumor groups.
  
  
  RESULTS
  In terms of CLM, the ZKSCAN3 overexpression was positively correlated with carcinoembryonic antigen (CEA), VEGF, and AKT expression. The protein-expression analysis showed that ZKSCAN-specific siRNA knockdown reduced CEA expression in LoVo and LS174T CRC cells. Matrigel invasion by ZKSCAN3-overexpressing HCT116 cells was increased when examined on CEA-coated filters compared with phosphate-buffered saline-treated controls. Additionally, matrix metalloproteinase 9 (MMP9) expression was greater in cells with reference allele (GG) than substitution allele (CC) for ZKSCAN3 rs733743 (p=0.032). ZKSCAN3 protein expression of the high serum CEA group was increased in hepatic metastatic tissue compared with the primary tumor tissue, while in the group with normal serum CEA it decreased or was similar. Reference ZKSCAN3 alleles were correlated with male dominance, a family history of malignancy, high serum CEA concentration and stage IV CRC in 450 patients with sporadic CRC. In conclusion, ZKSCAN3 appears to promote colorectal tumor progression and invasion. ZKSCAN3 may facilitate hepatic metastasis of CRC associated with CEA particularly in cases with CEA-producing tumor.
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Chan Wook
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Roh
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Ka Hee
authors.initials: KH
authors.lastname: Tak
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Bo Min
authors.initials: BM
authors.lastname: Koh
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Ha
authors.affiliation: Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Republic of Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
authors.affiliation: Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
authors.forename: Seon-Yong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, and Asan Medical Center, Seoul, Republic of Korea Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea jckim@amc.seoul.kr.
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
mesh_terms: D002272:Carcinoembryonic Antigen / Q000097:blood*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D002272:Carcinoembryonic Antigen; D014157:Transcription Factors; C530696:ZKSCAN3 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: CEA; Colorectal cancer; ZKSCAN3; liver metastasis