title: CATS (FAM64A) abnormal expression reduces clonogenicity of hematopoietic cells.
abstract: The CATS (FAM64A) protein interacts with CALM (PICALM) and the leukemic fusion protein CALM/AF10. CATS is highly expressed in leukemia, lymphoma and tumor cell lines and its protein levels strongly correlates with cellular proliferation in both malignant and normal cells. In order to obtain further insight into CATS function we performed an extensive analysis of CATS expression during differentiation of leukemia cell lines. While CATS expression decreased during erythroid, megakaryocytic and monocytic differentiation, a markedly increase was observed in the ATRA induced granulocytic differentiation. Lentivirus mediated silencing of CATS in U937 cell line resulted in somewhat reduced proliferation, altered cell cycle progression and lower migratory ability in vitro; however was not sufficient to inhibit tumor growth in xenotransplant model. Of note, CATS knockdown resulted in reduced clonogenicity of CATS-silenced cells and reduced expression of the self-renewal gene, GLI-1. Moreover, retroviral mediated overexpression of the murine Cats in primary bone marrow cells lead to decreased colony formation. Although our in vitro data suggests that CATS play a role in cellular processes important for tumorigenesis, such as cell cycle control and clonogenicity, these effects were not observed in vivo.
authors: Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil.
authors: Isabella
authors: I
authors: Barbutti
authors: Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil.
authors: Juliana M
authors: JM
authors: Xavier-Ferrucio
authors: Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil.
authors: João Agostinho
authors: JA
authors: Machado-Neto
authors: Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil.
authors: Lauremilia
authors: L
authors: Ricon
authors: Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Fabiola
authors: F
authors: Traina
authors: Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand.
authors: Stefan K
authors: SK
authors: Bohlander
authors: Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil.
authors: Sara Teresinha Olalla
authors: ST
authors: Saad
authors: Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil.|Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Leticia Fröhlich
authors: LF
authors: Archangelo
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009687:Nuclear Proteins; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C512398:PIMREG protein, human; D014212:Tretinoin
keywords: CALM/AF10; CATS (FAM64A); clonogenicity; leukemogenesis; proliferation