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

作者：Machado Neto Joao Agostinho; Lazarini Mariana; Favaro Patricia; Campos Paula de Melo; Scopim Ribeiro Renata; Franchi Junior Gilberto Carlos; Nowill Alexandre Eduardo; Moura Lima Paulo Roberto; Costa Fernando Ferreira; Benichou Serge; Olalla Saad Sara Teresinha; Traina Fabiola^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2015, 1853(3): 583-593.

DOI：10.1016/j.bbamcr.2014.12.012

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

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.

• 出版日期2015-3