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.
Highlights
The t(10;11)(p13;q14) translocation leads to the fusion of the CALM (PICALM) and AF10 genes [1]
While CATS expression decreased during erythroid, megakaryocytic and monocytic differentiation, a markedly increase was observed in the all-trans retinoic acid (ATRA) induced granulocytic differentiation
The expression of CALM/AF10 leads to the development of leukemia in murine bone marrow transplantation and transgenic models [9,10,11,12], and increasing evidence suggests that CALM/AF10 exerts its leukemogenic potential through transcriptional deregulation of target genes, including the HOXA gene cluster, interfering with normal hematopoietic differentiation [9, 13,14,15], through increased genomic instability by reducing global histone H3K79 methylation [16, 17] and through a novel proposed mechanism mediated by the CRM1dependent nuclear export pathway [18]
Summary
The t(10;11)(p13;q14) translocation leads to the fusion of the CALM (PICALM) and AF10 genes [1]. The expression of CALM/AF10 leads to the development of leukemia in murine bone marrow transplantation and transgenic models [9,10,11,12], and increasing evidence suggests that CALM/AF10 exerts its leukemogenic potential through transcriptional deregulation of target genes, including the HOXA gene cluster, interfering with normal hematopoietic differentiation [9, 13,14,15], through increased genomic instability by reducing global histone H3K79 methylation [16, 17] and through a novel proposed mechanism mediated by the CRM1dependent nuclear export pathway [18]. Whether CATS (FAM64A) contributes to leukemogenesis remains to be determined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
