PMID- 25201136 OWN - NLM STAT- MEDLINE DCOM- 20150702 LR - 20220409 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 45 IP - 6 DP - 2014 Dec TI - HP1beta suppresses metastasis of human cancer cells by decreasing the expression and activation of MMP2. PG - 2541-8 LID - 10.3892/ijo.2014.2646 [doi] AB - 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 HP1beta negatively regulates the expression and activation of matrix metallopeptidase (MMP)2, which mediates cancer metastasis by destructing type Ⅳ collagen. Reduced HP1beta expression correlates with the increased level of pro- and active-MMP2 in colon cancer cells. Consistently, HP1beta knockdown (KD) increased and HP1beta overexpression decreased the mRNA level of MMP2 and membrane type 1 metallopeptidase (MT1-MMP). Furthermore, cancer cells overexpressing HP1beta showed impaired migratory ability, whereas HP1beta‑deleted cancer cells had increased migration. HP1beta 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 HP1beta as a molecular regulator and an efficient therapeutic target of metastatic cancer. FAU - Yi, Sang Ah AU - Yi SA AD - Research Center for Epigenome Regulation, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 440‑746, Republic of Korea. FAU - Ryu, Hyun-Wook AU - Ryu HW AD - College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406‑840, Republic of Korea. FAU - Lee, Dong Hoon AU - Lee DH AD - College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406‑840, Republic of Korea. FAU - Han, Jeung-Whan AU - Han JW AD - Research Center for Epigenome Regulation, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 440‑746, Republic of Korea. FAU - Kwon, So Hee AU - Kwon SH AD - College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406‑840, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140909 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (CBX1 protein, human) RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (Histones) RN - 107283-02-3 (Chromobox Protein Homolog 5) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.80 (MMP14 protein, human) RN - EC 3.4.24.80 (Matrix Metalloproteinase 14) SB - IM MH - Cell Movement/*genetics MH - Chromobox Protein Homolog 5 MH - Chromosomal Proteins, Non-Histone/biosynthesis/*genetics MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Histones/genetics MH - Humans MH - MCF-7 Cells MH - Matrix Metalloproteinase 14/biosynthesis MH - Matrix Metalloproteinase 2/*biosynthesis MH - Neoplasm Invasiveness/*genetics MH - Neoplasm Metastasis MH - Neoplasms MH - Phosphatidylinositol 3-Kinases/biosynthesis MH - Signal Transduction EDAT- 2014/09/10 06:00 MHDA- 2015/07/03 06:00 CRDT- 2014/09/10 06:00 PHST- 2014/07/07 00:00 [received] PHST- 2014/08/26 00:00 [accepted] PHST- 2014/09/10 06:00 [entrez] PHST- 2014/09/10 06:00 [pubmed] PHST- 2015/07/03 06:00 [medline] AID - 10.3892/ijo.2014.2646 [doi] PST - ppublish SO - Int J Oncol. 2014 Dec;45(6):2541-8. doi: 10.3892/ijo.2014.2646. Epub 2014 Sep 9.