Silencing of casein kinase 2 inhibits PKC‑induced cell invasion by targeting MMP‑9 in MCF‑7 cells

Kim,Jeong‑Mi; Noh,Eun‑Mi; Song,Hyun‑Kyung; You,Yong‑Ouk; Jung,Sung Hoo; Kim,Jong‑Suk; Kwon,Kang‑Beom; Lee,Young‑Rae; Youn,Hyun Jo

doi:10.3892/mmr.2018.8885

Silencing of casein kinase 2 inhibits PKC‑induced cell invasion by targeting MMP‑9 in MCF‑7 cells

Authors:
- Jeong‑Mi Kim
- Eun‑Mi Noh
- Hyun‑Kyung Song
- Yong‑Ouk You
- Sung Hoo Jung
- Jong‑Suk Kim
- Kang‑Beom Kwon
- Young‑Rae Lee
- Hyun Jo Youn
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Affiliations: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeollabuk 570‑749, Republic of Korea, Department of Oral Biochemistry, School of Dentistry, Wonkwang University, Iksan, Jeollabuk 570‑749, Republic of Korea, Department of Surgery, Division of Breast and Thyroid Surgery, Chonbuk National University Medical School, Jeonju, Jeollabuk 560‑182, Republic of Korea, Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeollabuk 560‑182, Republic of Korea, Department of Korean Physiology, Wonkwang University School of Korean Medicine, Iksan, Jeonbuk 570‑749, Republic of Korea
Published online on: April 13, 2018 https://doi.org/10.3892/mmr.2018.8885
Pages: 8397-8402

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Abstract

Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been considered to represent an important factor in mammary tumorigenesis. Increased expression of matrix metalloproteinase‑9 (MMP‑9) via nuclear factor‑κB (NF‑κB) activation has been demonstrated to promote breast cancer cell invasion. In the present study, the involvement of CK2 in protein kinase C (PKC) induced cell invasion in MCF‑7 breast cancer cells was investigated as well as the underlying molecular mechanisms. The mRNA and protein levels of MMP‑9 in MCF‑7 cells were investigated using reverse transcription‑quantitative polymerase chain reaction, western blot analyses and a zymography assay. Cell invasiveness was investigated using a Matrigel invasion assay, and it was revealed that small interfering RNA specific for CK2 suppressed PKC induced cell invasion by regulating MMP‑9 expression via activation of the p38 kinase/c‑Jun N‑terminal kinase/NF‑κB pathway. In addition, it was demonstrated that CK2 inhibitors [apigenin (20 µM), emodin (20 µM) or 2‑dimethylamino‑4,5,6,7‑tetrabromo‑1H‑benzimidazole (2 µM)] suppressed PKC induced cell invasion and MMP‑9 expression. The results of the present study suggested that CK2 is an important factor involved in the induction of MCF‑7 breast cancer cell invasion by PKC. Therefore, CK2 may represent novel candidates for therapy intended to inhibit invasion in breast cancer.

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1	Munstermann U, Fritz G, Seitz G, Lu YP, Schneider HR and Issinger OG: Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue. Eur J Biochem. 189:251–257. 1990. View Article : Google Scholar : PubMed/NCBI
2	Ahmed K, Davis AT, Wang H, Faust RA, Yu S and Tawfic S: Significance of protein kinase CK2 nuclear signaling in neoplasia. J Cell Biochem Suppl. Suppl 35:S130–S135. 2000. View Article : Google Scholar
3	Ruzzene M and Pinna LA: Addiction to protein kinase CK2: A common denominator of diverse cancer cells? Biochim Biophys Acta. 1804:499–504. 2010. View Article : Google Scholar : PubMed/NCBI
4	Landesman-Bollag E, Romieu-Mourez R, Song DH, Sonenshein GE, Cardiff RD and Seldin DC: Protein kinase CK2 in mammary gland tumorigenesis. Oncogene. 20:3247–3257. 2001. View Article : Google Scholar : PubMed/NCBI
5	Christofori G: New signals from the invasive front. Nature. 441:444–450. 2006. View Article : Google Scholar : PubMed/NCBI
6	Chambers AF and Matrisian LM: Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 89:1260–1270. 1997. View Article : Google Scholar : PubMed/NCBI
7	Woodhouse EC, Chuaqui RF and Liotta LA: General mechanisms of metastasis. Cancer. 80 8 Suppl:S1529–S1537. 1997. View Article : Google Scholar
8	Patel D, Shukla S and Gupta S: Apigenin and cancer chemoprevention: Progress, potential and promise (review). Int J Oncol. 30:233–245. 2007.PubMed/NCBI
9	Shukla S and Gupta S: Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle. 6:1102–1114. 2007. View Article : Google Scholar : PubMed/NCBI
10	Shukla S and Gupta S: Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: Correlation with down-regulation of NF-kappaB-responsive genes. Clin Cancer Res. 10:3169–3178. 2004. View Article : Google Scholar : PubMed/NCBI
11	Chen D, Landis-Piwowar KR, Chen MS and Dou QP: Inhibition of proteasome activity by the dietary flavonoid apigenin is associated with growth inhibition in cultured breast cancer cells and xenografts. Breast Cancer Res. 9:R802007. View Article : Google Scholar : PubMed/NCBI
12	Way TD, Kao MC and Lin JK: Degradation of HER2/neu by apigenin induces apoptosis through cytochrome c release and caspase-3 activation in HER2/neu-overexpressing breast cancer cells. FEBS Lett. 579:145–152. 2005. View Article : Google Scholar : PubMed/NCBI
13	Kim JS, Eom JI, Cheong JW, Choi AJ, Lee JK, Yang WI and Min YH: Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia. Clin Cancer Res. 13:1019–1028. 2007. View Article : Google Scholar : PubMed/NCBI
14	Zhang L and Hung MC: Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Oncogene. 12:571–576. 1996.PubMed/NCBI
15	Zou J, Luo H, Zeng Q, Dong Z, Wu D and Liu L: Protein kinase CK2α is overexpressed in colorectal cancer and modulates cell proliferation and invasion via regulating EMT-related genes. J Transl Med. 9:972011. View Article : Google Scholar : PubMed/NCBI
16	Sarno S, Ruzzene M, Frascella P, Pagano MA, Meggio F, Zambon A, Mazzorana M, Di Maira G, Lucchini V and Pinna LA: Development and exploitation of CK2 inhibitors. Mol Cell Biochem. 274:69–76. 2005. View Article : Google Scholar : PubMed/NCBI
17	Di Maira G, Brustolon F, Bertacchini J, Tosoni K, Marmiroli S, Pinna LA and Ruzzene M: Pharmacological inhibition of protein kinase CK2 reverts the multidrug resistance phenotype of a CEM cell line characterized by high CK2 level. Oncogene. 26:6915–6926. 2007. View Article : Google Scholar : PubMed/NCBI
18	Pagano MA, Andrzejewska M, Ruzzene M, Sarno S, Cesaro L, Bain J, Elliott M, Meggio F, Kazimierczuk Z and Pinna LA: Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 47:6239–6247. 2004. View Article : Google Scholar : PubMed/NCBI
19	Nakajima M, Welch DR, Belloni PN and Nicolson GL: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res. 47:4869–4876. 1987.PubMed/NCBI
20	Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI
21	Lin CW, Hou WC, Shen SC, Juan SH, Ko CH, Wang LM and Chen YC: Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis. 29:1807–1815. 2008. View Article : Google Scholar : PubMed/NCBI
22	Lee SO, Jeong YJ, Im HG, Kim CH, Chang YC and Lee IS: Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells. Biochem Biophys Res Commun. 354:165–171. 2007. View Article : Google Scholar : PubMed/NCBI
23	Newton AC: Regulation of protein kinase C. Curr Opin Cell Biol. 9:161–167. 1997. View Article : Google Scholar : PubMed/NCBI
24	Lee SO, Jeong YJ, Kim M, Kim CH and Lee IS: Suppression of PMA-induced tumor cell invasion by capillarisin via the inhibition of NF-kappaB-dependent MMP-9 expression. Biochem Biophys Res Commun. 366:1019–1024. 2008. View Article : Google Scholar : PubMed/NCBI
25	Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG and Kim CH: Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: Complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J. 18:1670–1681. 2004. View Article : Google Scholar : PubMed/NCBI
26	Hong S, Park KK, Magae J, Ando K, Lee TS, Kwon TK, Kwak JY, Kim CH and Chang YC: Ascochlorin inhibits matrix metalloproteinase-9 expression by suppressing activator protein-1-mediated gene expression through the ERK1/2 signaling pathway: Inhibitory effects of ascochlorin on the invasion of renal carcinoma cells. J Biol Chem. 280:25202–25209. 2005. View Article : Google Scholar : PubMed/NCBI
27	Woo MS, Jung SH, Kim SY, Hyun JW, Ko KH, Kim WK and Kim HS: Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells. Biochem Biophys Res Commun. 335:1017–1025. 2005. View Article : Google Scholar : PubMed/NCBI
28	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
29	Ohashi Y, Tsuchiya Y, Koizumi K, Sakurai H and Saiki I: Prevention of intrahepatic metastasis by curcumin in an orthotopic implantation model. Oncology. 65:250–258. 2003. View Article : Google Scholar : PubMed/NCBI
30	Reyes-Ortiz CA, Eschbach K, Zhang DD and Goodwin JS: Neighborhood composition and cancer among hispanics: Tumor stage and size at time of diagnosis. Cancer Epidemiol Biomarkers Prev. 17:2931–2936. 2008. View Article : Google Scholar : PubMed/NCBI
31	Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z and Mariotto A: SEER cancer statistics review, 1975–2014. National Cancer Institute; Bethesda, MD: 2017
32	Polyak K: Heterogeneity in breast cancer. J Clin Invest. 121:3786–3788. 2011. View Article : Google Scholar : PubMed/NCBI
33	Neophytou C, Boutsikos P and Papageorgis P: Molecular mechanisms and emerging therapeutic targets of triple-negative breast cancer metastasis. Front Oncol. 8:312018. View Article : Google Scholar : PubMed/NCBI
34	Deryugina EI and Quigley JP: Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 25:9–34. 2006. View Article : Google Scholar : PubMed/NCBI
35	Li DM and Feng YM: Signaling mechanism of cell adhesion molecules in breast cancer metastasis: Potential therapeutic targets. Breast Cancer Res Treat. 128:7–21. 2011. View Article : Google Scholar : PubMed/NCBI
36	Scorilas A, Karameris A, Arnogiannaki N, Ardavanis A, Bassilopoulos P, Trangas T and Talieri M: Overexpression of matrix-metalloproteinase-9 in human breast cancer: A potential favourable indicator in node-negative patients. Br J Cancer. 84:1488–1496. 2001. View Article : Google Scholar : PubMed/NCBI
37	Park SK, Hwang YS, Park KK, Park HJ, Seo JY and Chung WY: Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells. Carcinogenesis. 30:1225–1233. 2009. View Article : Google Scholar : PubMed/NCBI
38	Weng CJ, Chau CF, Hsieh YS, Yang SF and Yen GC: Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kappaB and AP-1. Carcinogenesis. 29:147–156. 2008. View Article : Google Scholar : PubMed/NCBI
39	Eberhardt W, Huwiler A, Beck KF, Walpen S and Pfeilschifter J: Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J Immunol. 165:5788–5797. 2000. View Article : Google Scholar : PubMed/NCBI
40	Yao J, Xiong S, Klos K, Nguyen N, Grijalva R, Li P and Yu D: Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells. Oncogene. 20:8066–8074. 2001. View Article : Google Scholar : PubMed/NCBI
41	Madrid LV, Mayo MW, Reuther JY and Baldwin AS Jr: Akt stimulates the transactivation potential of the RelA/p65 Subunit of NF-kappa B through utilization of the Ikappa B kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem. 276:18934–18940. 2001. View Article : Google Scholar : PubMed/NCBI
42	Saja K, Babu MS, Karunagaran D and Sudhakaran PR: Anti-inflammatory effect of curcumin involves downregulation of MMP-9 in blood mononuclear cells. Int Immunopharmacol. 7:1659–1667. 2007. View Article : Google Scholar : PubMed/NCBI