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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

ANKHD1 silencing inhibits Stathmin 1 activity, cell proliferation and migration of leukemia cells

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Machado-Neto, Joao Agostinho [1] ; Lazarini, Mariana [1] ; Favaro, Patricia [1] ; Campos, Paula de Melo [1] ; Scopim-Ribeiro, Renata [1] ; Franchi Junior, Gilberto Carlos [2] ; Nowill, Alexandre Eduardo [2] ; Moura Lima, Paulo Roberto [1] ; Costa, Fernando Ferreira [1] ; Benichou, Serge [3] ; Olalla Saad, Sara Teresinha [1] ; Traina, Fabiola [1]
Total Authors: 12
[1] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Hemoctr Unicamp, Inst Nacl Ciencia & Tecnol Sangue, BR-13083878 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Integrated Ctr Childhood Oncohematol Invest, BR-13083878 Campinas, SP - Brazil
[3] Inst Cochin, INSERM, U1016, Paris - France
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 10

ANKHD1 is highly expressed inhuman acute leukemia cells and potentially regulates multiple cellular functions through its ankyrin-repeat domains. In order to identify interaction partners of the ANKHD1 protein and its role in leukemia cells, we performed a yeast two-hybrid system screen and identified SIVA, a cellular protein known to be involved in proapoptotic signaling pathways. The interaction between ANKHD1 and SNA was confirmed by co-imunoprecipitation assays. Using human leukemia cell models and lentivirus-mediated shRNA approaches, we showed that ANKHD1 and SIVA proteins have opposing effects. While it is known that SIVA silencing promotes Stathmin 1 activation, increased cell migration and xenograft tumor growth, we showed that ANKHD1 silencing leads to Stathmin 1 inactivation, reduced cell migration and xenograft tumor growth, likely through the inhibition of SIVA/Stathmin 1 association. In addition, we observed that ANKHD1 knockdown decreases cell proliferation, without modulating apoptosis of leukemia cells, while SIVA has a proapoptotic function in U937 cells, but does not modulate proliferation in vitro. Results indicate that ANKHD1 binds to SIVA and has an important role in inducing leukemia cell proliferation and migration via the Stathmin 1 pathway. ANKHD1 may be an oncogene and participate in the leukemia cell phenotype. (C) 2014 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 09/00268-8 - Study of the function of ANKHD1 in apoptosis and its interaction with SIVA in cancer cells
Grantee:Fabíola Traina
Support type: Regular Research Grants
FAPESP's process: 12/09982-8 - Investigation of molecular alterations in myeloid neoplasms.
Grantee:Fabíola Traina
Support type: Regular Research Grants
FAPESP's process: 11/51959-0 - Biology of neoplastic diseases of bone marrow
Grantee:Sara Teresinha Olalla Saad
Support type: Research Projects - Thematic Grants
FAPESP's process: 11/06840-5 - Study of ANKHD1 function on the proliferation, apoptosis and cell cycle in hematological neoplasia
Grantee:João Agostinho Machado Neto
Support type: Scholarships in Brazil - Doctorate