ENO1 Contributes to Cell Proliferation and Invasion in Burkitt's Lymphoma

Abstract：

Burkitt's lymphoma is a highly aggressive B-cell non-Hodgkin's lymphoma which is characterized by excessive proliferation of the malignant cells and deregulation of the c-MYC gene. However, the mechanisms underlying the aggressive behavior of Burkitt's lymphoma remain largely elusive. By analyzing the secretome of Burkitt's lymphoma cell line Daudi, we identified alpha-enolase (ENO1) was substantially upregulated in the conditional media of Daudi cells. We confirmed that the expression of ENO1 in patients with Burkitt's lymphoma was increased by qPCR and Western blot assays. CCK-8 and transwell assays revealed that knockdown of ENO1 in Burkitt's lymphoma cell lines Daudi and Raji inhibited cell proliferation and invasion. Further, in the mouse models,hematoxylin-eosin staining and flow cytomery revealed that knockdown of ENO1 inhibited the progression and invasion of tumors and delay the onset time of mice.

ENO1 is an important glycolytic enzyme which has been found to be overexpressed in multiple solid tumors and promote cell proliferation, migration and invasion in tumors. We confirmed that knowndown of ENO1 reduced the binding of plasminogen on cell membrane by flow cytometry. In addition, silencing ENO1 effectively blocked the fibrinolytic activity. These results suggested ENO1 might contribute to Burkitt's lymphoma invasion by recruiting and activating plasminogen on the surface of Burkitt's lymphoma cells. We also found PI3K/AKT/mTOR pathway and N-cadherin, vimentin, slug were inhibited in response to the reduction of ENO1. We also found that c-Myc can bind to the promoter of ENO1 and promote the expression of ENO1 in Burkitt's lymphoma cell lines.

Altogether, these results not only reveal the role and mechanism of ENO1 in the development of Burkitt's lymphoma, but also highlight ENO1 as a potential therapeutic target in the treatment of Burkitt's lymphoma.

Key words: Burkitt's Lmphoma , ENO1, c-MYC, PLG, Invasion

No relevant conflicts of interest to declare.