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Biochim Biophys Acta. 2015 Mar;1853(3):583-93. doi: 10.1016/j.bbamcr.2014.12.012. Epub 2014 Dec 16.

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

Author information

1
Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas 13083-878, São Paulo, Brazil.
2
Integrated Center for Childhood Onco-Hematological Investigation, University of Campinas, Campinas 13083-878, São Paulo, Brazil.
3
INSERM U1016, Institut Cochin, Paris, France.
4
Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas 13083-878, São Paulo, Brazil. Electronic address: ftraina@fmrp.usp.br.

Abstract

ANKHD1 is highly expressed in human 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 SIVA 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.

KEYWORDS:

ANKHD1; Acute leukemia; Cell proliferation; SIVA1; Stathmin 1

PMID:
25523139
DOI:
10.1016/j.bbamcr.2014.12.012
[Indexed for MEDLINE]
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