Abstract
BackgroundBurkitt’s lymphoma is an aggressive malignancy with high risk of metastasis to extranodal sites, such as bone marrow and central nervous system. The prognosis of metastatic Burkitt’s lymphoma is poor. Here we sought to identify a role of histone deacetylase 6 (HDAC6) in the metastasis of Burkitt’s lymphoma cells.MethodsBurkitt’s lymphoma cells were pharmacologically treated with niltubacin, tubacin or sodium butyrate (NaB) or transfected with siRNAs to knock down the expression of HDAC6. Cell migration and invasion ability were measured by transwell assay, and cell cycle progression was analyzed by flow cytometry. Cell adhesion and proliferation was determined by CellTiter-Glo luminescent cell viability assay kit. Cell morphological alteration and microtubule stability were analyzed by immunofluorescence staining. Effect of niltubacin, tubacin and NaB on acetylated tubulin and siRNA efficacy were measured by western blotting.ResultsSuppression of histone deacetylase 6 activity significantly compromised the migration and invasion of Burkitt’s lymphoma cells, without affecting cell proliferation and cell cycle progression. Mechanistic study revealed that HDAC6 modulated chemokine induced cell shape elongation and cell adhesion probably through its action on microtubule dynamics.ConclusionsWe identified a critical role of HDAC6 in the metastasis of Burkitt’s lymphoma cells, suggesting that pharmacological inhibition of HDAC6 could be a promising strategy for the management of metastatic Burkitt’s lymphoma.
Highlights
Burkitt? s lymphoma is an aggressive malignancy with high risk of metastasis to extranodal sites, such as bone marrow and central nervous system
Firstly we investigated the role of histone deacetylase 6 (HDAC6) in Burkitt? s lymphoma (BL) cell motility
As cell attachment to endothelium or extracellular matrix (ECM) is prerequisite for malignant cell infiltration to the destined sites, we examined whether HDAC6 regulates cell motility via its action on cell adhesion
Summary
Burkitt? s lymphoma is an aggressive malignancy with high risk of metastasis to extranodal sites, such as bone marrow and central nervous system. S lymphoma is an aggressive malignancy with high risk of metastasis to extranodal sites, such as bone marrow and central nervous system. We sought to identify a role of histone deacetylase 6 (HDAC6) in the metastasis of Burkitt? S lymphoma (BL) as a highly aggressive B-cell malignancy, usually occurs in adolescent as well as in patients with immune defect. Most of the childhood BL is effectively managed with the cyclical intensive chemotherapy [4]. Another feature of BL is its high aggression, occasionally disseminates to bone marrow (BM) and central nervous system (CNS), contributing to poor prognosis in clinics [5]. Attempts to explore better regimens to inhibit the metastasis of BL is urgently needed
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