Lpxn Regulates Proliferation, Adhesion and Invasion of Acute Myeloid Leukemic Cells

Leupaxin (LPXN) belongs to the focal adhesion-associated adaptor protein family, participating in regulating cell adhesion and metastasis. LPXN is a recurrent fusion partner in translocations identified in AML, namely t(11;12) and t(11;21), highlights its potential leukemogenic role in acute myeloid leukemia (AML). However, the precise mechanisms by which LPXN participate in the pathogenesis and progression of AML remains unknown. In the present study, we found that LPXN had a wide expression among a variety of hematological malignancies, including AML. Stable overexpression of LPXN in K-562 cells highlighted the proliferation advantage induced by this gene observed via colony-forming-assay and nude mice models. Proliferation was believed to be induced by LPXN-driven upregulation of ERK1/2 and pERK1/2 in K562-LPXN cells. Moreover, LPXN-expressing K-562 cells were less inhibited by arsenic trioxide, as compared with control cells, which might due to downregulation of BAX, FAS and upregulation of BCL-2. Adhesion to fibronectin and invasion across matrigel were modulated by overexpression and knockdown of LPXN, respectively. Similarly, activity of MMP-9 and MMP-2, and expression of integrin α4, α5 and β1, correlated with overexpression or silencing of LPXN, respectively. Expression of pP38 also showed a positive correlation with LPXN. In general, our data suggests that LPXN promotes proliferation in vitro and in vivo via the MAPK pathway, as well as enhances adhesion and invasion of AML cells through modulating expression of integrin α4, α5, β1 and MMP-9/MMP-2.