Histone demethylase KDM6B inhibits breast cancer metastasis by regulating Wnt/β-catenin signaling

FEBS Open Bio. 2021 Aug;11(8):2273-2281. doi: 10.1002/2211-5463.13236. Epub 2021 Jul 12.

Abstract

Tumor metastasis remains a major challenge for patients with breast cancer. Aberrant epigenetic factor lysine-specific demethylase 6B (KDM6B) has been associated with tumor progression. Here, we show that KDM6B is significantly down-regulated in human breast cancer tissues, and its low expression is associated with poor prognosis of patients with breast cancer. Furthermore, overexpression of KDM6B remarkably inhibited cell proliferation, invasion, migration and epithelial-mesenchymal transition markers of breast cancer cells in vitro and tumor growth and lung metastasis in vivo. Notably, the expression of KDM6B in breast cancer tissues was negatively correlated with that of β-catenin, and overexpression of KDM6B decreased the expression of β-catenin and its accumulation in the nucleus of breast cancer cells. Overall, our findings provide novel insights into suppression of metastasis of breast cancer cells by KDM6B via β-catenin and suggest involvement of the KDM6B-Wnt/β-catenin axis in breast cancer progression.

Keywords: KDM6B; Wnt/β-catenin signaling; breast cancer; metastasis.