CATS (FAM64A) abnormal expression reduces clonogenicity of hematopoietic cells

// Isabella Barbutti 1 , Juliana M. Xavier-Ferrucio 1, * , Joao Agostinho Machado-Neto 1, # , Lauremilia Ricon 1 , Fabiola Traina 2 , Stefan K. Bohlander 3 , Sara Teresinha Olalla Saad 1 , Leticia Frohlich Archangelo 1, 4 1 Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Carlos Chagas 480, Campinas-SP, Brazil 2 Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil 3 Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand 4 Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil * Present address: Department of Laboratory Medicine, Yale Stem Cell Center # Present address: Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil Correspondence to: Leticia Frohlich Archangelo, email: leticiafa@fmrp.usp.br Keywords: CATS (FAM64A), proliferation, clonogenicity, CALM/AF10, leukemogenesis Received: November 10, 2015 Accepted: August 21, 2016 Published: August 31, 2016 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 .