CATS (FAM64A) abnormal expression reduces clonogenicity of hematopoietic cells

Author(s)

Barbutti, Isabella ; Xavier-Ferrucio, Juliana M. ; Machado-Neto, Joao Agostinho ; Ricon, Lauremilia ; Traina, Fabiola ; Bohlander, Stefan K. ; Olalla Saad, Sara Teresinha ; Archangelo, Leticia Frohlich

• Document type: Journal article
• Source: ONCOTARGET; v. 7, n. 42, p. 68385-68396, OCT 18 2016.
• Web of Science Citations: 4

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. (AU)

• FAPESP's process: 11/51959-0 - Biology of neoplastic diseases of bone marrow
• Grantee: Sara Teresinha Olalla Saad
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/18188-0 - Effects of CATS (FAM64A) depletion and overexpression on the proliferation of the leukemic cell line U937
• Grantee: Isabella Barbutti Gonçalves
• Support Opportunities: Scholarships in Brazil - Scientific Initiation