Bone sialoprotein facilitates anoikis resistance in lung cancer by inhibiting miR-150-5p expression

Abstract

Metastatic lung cancer is a highly prevalent cancer with a very low chance of long-term survival. Metastasis at secondary sites requires that cancer cells develop anoikis resistance to survive during circulation. High levels of bone sialoprotein (BSP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs), have been shown to promote the spread of lung cancer cells; however, the effects of BSP in anoikis resistance are largely unknown. In this study, we determined that BSP promotes anoikis resistance in lung cancer cells. BSP was also shown to promote the expression of E-cadherin and vimentin (epithelial-to-mesenchymal transition markers, which have been utilized as indicators of anoikis resistance). It appears that BSP facilitates MMP-14-dependent anoikis resistance by inhibiting the synthesis of miR-150-5p and activating the ERK signalling pathway. Knockdown of BSP expression was shown to block lung cancer metastasis by lowering anoikis resistance in vivo. These results indicate that BSP is a promising target to deal with anoikis resistance and metastasis in human lung cancers.