BMP-6 inhibits the metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression Corrigendum in /10.3892/or.2024.8822

Hu,Fen; Zhang,Yunfeng; Li,Mi; Zhao,Lina; Chen,Jing; Yang,Shuang; Zhang,Xiujun

doi:10.3892/or.2015.4540

BMP-6 inhibits the metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression

Corrigendum in: /10.3892/or.2024.8822

Authors:
- Fen Hu
- Yunfeng Zhang
- Mi Li
- Lina Zhao
- Jing Chen
- Shuang Yang
- Xiujun Zhang
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Affiliations: College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China, Medical College of Nankai University, Tianjin 300071, P.R. China, College of Psychology, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China
Published online on: December 31, 2015 https://doi.org/10.3892/or.2015.4540
Pages: 1823-1830

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Abstract

Bone morphogenetic protein-6 (BMP-6) is a multifunctional molecule with distinct abilities in embryogenesis and organogenesis. In the present study, our results showed that the rate of BMP-6-negative expression was 30.56% in breast cancer tissues, but was 9.58% in normal tissues by immunohistochemical staining. This implied that BMP-6 expression is absent in breast cancer tissues and may suppress breast cancer metastasis. In addition, stable overexpression of BMP-6 in MDA-MB‑231 cells was established to analyze the metastatic ability. The Boyden chamber assay showed that BMP-6 inhibited the migration and invasion of MDA-MB-231 cells. Moreover, real-time PCR analysis showed that BMP-6 markedly downregulated matrix metalloproteinase-1 (MMP-1) expression at both the mRNA and protein levels in the MDA-MB‑231 cells. Importantly, the results of luciferase and CHIP assays revealed that BMP-6 inhibited MMP-1 promoter activity through the AP-1 response element. In MDA-MB-231 cells treated with BMP-6, a significant decrease in the recruitment of AP-1 components, c-Jun/c-Fos, to the endogenous MMP-1 promoter was noted. We also demonstrated that BMP-6 inhibited the invasion of MDA-MB-231 cells, and this effect was significantly attenuated by overexpression of MMP-1. In contrast, MMP-1 knockdown by RNA interference or MMP-1 inhibitor exhibited an opposite effect. These observations suggest a novel role of BMP-6 in the inhibition of breast cancer metastasis by regulating secretion of MMPs in the tumor microenvironment.

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1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
2	Liotta LA, Steeg PS and Stetler-Stevenson WG: Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell. 64:327–336. 1991. View Article : Google Scholar : PubMed/NCBI
3	Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–364. 1996. View Article : Google Scholar : PubMed/NCBI
4	Nabeshima K, Inoue T, Shimao Y and Sameshima T: Matrix metalloproteinases in tumor invasion: Role for cell migration. Pathol Int. 52:255–264. 2002. View Article : Google Scholar : PubMed/NCBI
5	Duffy MJ: The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis. 10:145–155. 1992. View Article : Google Scholar : PubMed/NCBI
6	Sreenath T, Matrisian LM, Stetler-Stevenson W, Gattoni-Celli S and Pozzatti RO: Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential. Cancer Res. 52:4942–4947. 1992.PubMed/NCBI
7	Chabottaux V and Noel A: Breast cancer progression: Insights into multifaceted matrix metalloproteinases. Clin Exp Metastasis. 24:647–656. 2007. View Article : Google Scholar : PubMed/NCBI
8	Egeblad M and Werb Z: New functions for the matrix metallopro-teinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI
9	Liu H, Kato Y, Erzinger SA, Kiriakova GM, Qian Y, Palmieri D, Steeg PS and Price JE: The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model. BMC Cancer. 12:5832012. View Article : Google Scholar : PubMed/NCBI
10	Hu F, Wang C, Guo S, Sun W, Mi D, Gao Y, Zhang J, Zhu T and Yang S: δEF1 promotes osteolytic metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression. Biochim Biophys Acta. 1809:200–210. 2011. View Article : Google Scholar : PubMed/NCBI
11	Tang SJ, Hoodless PA, Lu Z, Breitman ML, McInnes RR, Wrana JL and Buchwald M: The Tlx-2 homeobox gene is a downstream target of BMP signalling and is required for mouse mesoderm development. Development. 125:1877–1887. 1998.PubMed/NCBI
12	Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI
13	Yang S, Du J, Wang Z, Yuan W, Qiao Y, Zhang M, Zhang J, Gao S, Yin J, Sun B, et al: BMP-6 promotes E-cadherin expression through repressing deltaEF1 in breast cancer cells. BMC Cancer. 7:2112007. View Article : Google Scholar : PubMed/NCBI
14	Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI
15	Wang C, Hu F, Guo S, Mi D, Shen W, Zhang J, Qiao Y, Zhu T and Yang S: BMP-6 inhibits MMP-9 expression by regulating heme oxygenase-1 in MCF-7 breast cancer cells. J Cancer Res Clin Oncol. 137:985–995. 2011. View Article : Google Scholar
16	Bendrik C, Robertson J, Gauldie J and Dabrosin C: Gene transfer of matrix metalloproteinase-9 induces tumor regression of breast cancer in vivo. Cancer Res. 68:3405–3412. 2008. View Article : Google Scholar : PubMed/NCBI
17	Yan JD, Yang S, Lü SJ, Lei RY and Zhu TH: Expression of recombinant human BMP6 in CHO cells by fused to the signal peptide and propeptide of another homologue protein. Sheng Wu Gong Cheng Xue Bao. 23:413–417. 2007.In Chinese. View Article : Google Scholar : PubMed/NCBI
18	Xia Y, Yu PB, Sidis Y, Beppu H, Bloch KD, Schneyer AL and Lin HY: Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4. J Biol Chem. 282:18129–18140. 2007. View Article : Google Scholar : PubMed/NCBI
19	Peng Z, Fernandez P, Wilder T, Yee H, Chiriboga L, Chan ES and Cronstein BN: Ecto-5′-nucleotidase (CD73)-mediated extracellular adenosine production plays a critical role in hepatic fibrosis. Nucleosides Nucleotides Nucleic Acids. 27:821–824. 2008. View Article : Google Scholar : PubMed/NCBI
20	Fukui T, Suga T, Iida RH, Morito M, Luan X, Diekwisch TG, Nakamura Y and Yamane A: BMP-2 regulates the formation of oral sulcus in mouse tongue by altering the balance between TIMP-1 and MMP-13. Anat Rec. 293:1408–1415. 2010. View Article : Google Scholar
21	Nagase H, Visse R and Murphy G: Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 69:562–573. 2006. View Article : Google Scholar : PubMed/NCBI
22	Du J, Yang S, An D, Hu F, Yuan W, Zhai C and Zhu T: BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1. Cell Res. 19:487–496. 2009. View Article : Google Scholar : PubMed/NCBI
23	Oxmann D, Held-Feindt J, Stark AM, Hattermann K, Yoneda T and Mentlein R: Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype. Oncogene. 27:3567–3575. 2008. View Article : Google Scholar : PubMed/NCBI
24	Nagaiah G and Abraham J: Circulating tumor cells in the management of breast cancer. Clin Breast Cancer. 10:209–216. 2010. View Article : Google Scholar : PubMed/NCBI
25	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI
26	Yang S, Du J, Wang Z, Yan J, Yuan W, Zhang J and Zhu T: Dual mechanism of deltaEF1 expression regulated by bone morphogenetic protein-6 in breast cancer. Int J Biochem Cell Biol. 41:853–861. 2009. View Article : Google Scholar
27	Funahashi J, Kamachi Y, Goto K and Kondoh H: Identification of nuclear factor delta EF1 and its binding site essential for lens-specific activity of the delta 1-crystallin enhancer. Nucleic Acids Res. 19:3543–3547. 1991. View Article : Google Scholar : PubMed/NCBI
28	Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H and Foisner R: DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 24:2375–2385. 2005. View Article : Google Scholar : PubMed/NCBI