title: Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo.
abstract: BACKGROUND
  Membrane-bound phospholipid scramblase 1 (PLSCR1) is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas (CRCs). In the present study, we investigated the tumorigenic role of PLSCR1 in CRC and suggest that it is a potential therapeutic target.
  
  
  METHODS
  To identify PLSCR1 as a therapeutic target, we studied the tumorigenic properties of CRC cell lines treated with a monoclonal antibody (NP1) against the N-terminus of PLSCR1 in vitro and in vivo. We also investigated cell cycle status and epidermal growth factor receptor-related pathways and downstream effectors of PLSCR1 after blocking its function with NP1.
  
  
  RESULTS
  Treating CRC cells with NP1 in vitro and in vivo decreased cell proliferation, anchorage-independent growth, migration, and invasion. Adding NP1 to the CRC cell line HT29 caused arrest at G1/S. Treating HT29 cells with NP1 significantly decreased the expression of cyclin D1 and phosphorylation levels of Src, the adaptor protein Shc, and Erks. The reduced level of cyclin D1 led to an increase in the activated form of the tumor suppressor retinoblastoma protein via dephosphorylation. These actions led to attenuation of tumorigenesis.
  
  
  CONCLUSIONS
  Therefore, PLSCR1 may serve as a potential therapeutic target for CRC.
authors.affiliation: Department of Colorectal Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chung-Wei
authors.initials: CW
authors.lastname: Fan
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Kuei-Tien
authors.initials: KT
authors.lastname: Chen
authors.forename: Chia-Rui
authors.initials: CR
authors.lastname: Shen
authors.forename: Yung-Bin
authors.initials: YB
authors.lastname: Kuo
authors.forename: Ya-Shan
authors.initials: YS
authors.lastname: Chen
authors.forename: Yeh-Pin
authors.initials: YP
authors.lastname: Chou
authors.forename: Wei-Shan
authors.initials: WS
authors.lastname: Wei
authors.forename: Err-Cheng
authors.initials: EC
authors.lastname: Chan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D046888:Tissue Array Analysis; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D049294:Phospholipid Transfer Proteins; D066246:ErbB Receptors