HP1β suppresses metastasis of human cancer cells by decreasing the expression and activation of MMP2

Abstract

Heterochromatin protein 1 (HP1) is an epigenetic modifier of gene regulation and chromatin packing via binding to trimethylated histone H3 lysine 9 (H3K9). HP1 plays an important role in gene activation as well as gene repression in heterochromatin and euchromatin. However, the role of individual HP1 proteins in human diseases remains elusive. Here, we show that HP1ß negatively regulates the expression and activation of matrix metallopeptidase (MMP)2, which mediates cancer metastasis by destructing type IV collagen. Reduced HP1ß expression correlates with the increased level of pro- and active-MMP2 in colon cancer cells. Consistently, HP1ß knockdown (KD) increased and HP1ß overexpression decreased the mRNA level of MMP2 and membrane type 1 metallopeptidase (MT1-MMP). Furthermore, cancer cells overexpressing HP1ß showed impaired migratory ability, whereas HP1ß-deleted cancer cells had increased migration. HP1ß negatively regulates MMP2 expression in a transcriptional level and prevents MMP2 activation through reducing the expression of MT1-MMP. These findings shed new light on HP1ß as a molecular regulator and an efficient therapeutic target of metastatic cancer.