title: 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 HP1β negatively regulates the expression and activation of matrix metallopeptidase (MMP)2, which mediates cancer metastasis by destructing type Ⅳ collagen. Reduced HP1β expression correlates with the increased level of pro- and active-MMP2 in colon cancer cells. Consistently, HP1β knockdown (KD) increased and HP1β overexpression decreased the mRNA level of MMP2 and membrane type 1 metallopeptidase (MT1-MMP). Furthermore, cancer cells overexpressing HP1β showed impaired migratory ability, whereas HP1β‑deleted cancer cells had increased migration. HP1β 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 HP1β as a molecular regulator and an efficient therapeutic target of metastatic cancer.
authors.affiliation: Research Center for Epigenome Regulation, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 440‑746, Republic of Korea.
authors.forename: Sang Ah
authors.initials: SA
authors.lastname: Yi
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Research Center for Epigenome Regulation, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 440‑746, Republic of Korea.
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kwon
mesh_terms: D002465:Cell Movement / Q000235:genetics*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D009369:Neoplasms; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D015398:Signal Transduction
chemical_list: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D019869:Phosphatidylinositol 3-Kinases; C000715593:CBX1 protein, human; C507086:MMP14 protein, human