Serum- and glucocorticoid-regulated protein kinase 3 overexpression promotes tumor development and aggression in breast cancer cells

Sun,Xiaojie; Liu,Xiucai; Liu,Bo; Li,Shuyan; Zhang,Dongmei; Guo,Hongyan

doi:10.3892/ol.2016.4638

Serum- and glucocorticoid-regulated protein kinase 3 overexpression promotes tumor development and aggression in breast cancer cells

Authors:
- Xiaojie Sun
- Xiucai Liu
- Bo Liu
- Shuyan Li
- Dongmei Zhang
- Hongyan Guo
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Affiliations: Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Respiratory Medicine, Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Qiqihar Medical University Library, Qiqihar, Heilongjiang 161006, P.R. China
Published online on: May 26, 2016 https://doi.org/10.3892/ol.2016.4638
Pages: 437-444
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Serum- and glucocorticoid-regulated protein kinase 3 (SGK3) is critical for tumor survival, proliferation and invasion. In the present study we evaluated SGK3 expression in breast tissues and investigated alterations in SGK3 levels in tumor multiplication, progression and apoptosis. Tissue microarray analyses were performed to examine SGK3 expression in breast cancer samples, as well as in adjacent noncancerous and normal tissues. The pEGFP‑N1‑SGK3 plasmid was transfected into MDA‑MB‑231 cells to generate SGK3‑overexpressing cells. Cell growth assays, colony formation assays, cell cycle analyses, horizontal and vertical migration tests, reverse transcription‑polymerase chain reaction and western blot assays were employed to investigate the biological behavior of SGK3‑overexpressing cells. SGK3 levels were significantly higher in breast cancer samples compared with adjacent noncancerous and normal tissues. Cell growth curves revealed increased proliferation and decreased apoptosis in SGK3-overexpressing cells. SGK3-overexpressing cells also demonstrated enhanced invasion and migration abilities. SGK3‑overexpressing cells had high levels of an apoptosis-related gene (bcl‑xl) and invasion‑related genes (mmp2 and mmp9), and decreased levels of an anti‑apoptosis gene (bad). Phosphorylation of GSK‑3β, which is downstream in the phosphoinositide 3‑kinase signaling pathway, was activated by SGK3 overexpression. β‑catenin phosphorylation did not differ between the SGK3‑overexpressing and non-SGK3-overexpressing cells. SGK3 overexpression induces GSK‑3β phosphorylation, enhancing apoptosis‑ and invasion‑related genes and proteins and thereby leading to tumor development and aggression in breast cancer cells.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Li Y, Drabsch Y, Pujuguet P, Ren J, van Laar T, Zhang L, van Dam H, Clément-Lacroix P and Ten Dijke P: Genetic depletion and pharmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models. Breast Cancer Res. 17:282015. View Article : Google Scholar : PubMed/NCBI
3	Lu D, Zhou X, Yao L, Liu C, Jin F and Wu Y: Clinical implications of the interleukin 27 serum level in breast cancer. J Investig Med. 62:627–631. 2014. View Article : Google Scholar : PubMed/NCBI
4	Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI
5	Liu P, Cheng H, Roberts TM and Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 8:627–644. 2009. View Article : Google Scholar : PubMed/NCBI
6	Kobayashi T, Deak M, Morrice N and Cohen P: Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J. 344:189–197. 1999. View Article : Google Scholar : PubMed/NCBI
7	Vasudevan KM, Barbie DA, Davies MA, Rabinovsky R, McNear CJ, Kim JJ, Hennessy BT, Tseng H, Pochanard P, Kim SY, et al: AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer. Cancer Cell. 16:21–32. 2009. View Article : Google Scholar : PubMed/NCBI
8	Wang Y, Zhou D, Phung S, Masri S, Smith D and Chen S: SGK3 is an estrogen-inducible kinase promoting estrogen-mediated survival of breast cancer cells. Mol Endocrinol. 25:72–82. 2011. View Article : Google Scholar : PubMed/NCBI
9	Shi L, Wang K, Zhao M, Yuan X and Huang C: Overexpression of PIP5KL1 suppresses the growth of human cervical cancer cells in vitro and in vivo. Cell Biol Int. 34:309–315. 2010. View Article : Google Scholar : PubMed/NCBI
10	Xu J, Wan M, He Q, Bassett RL Jr, Fu X, Chen AC, Shi F, Creighton CJ, Schiff R, Huo L and Liu D: SGK3 is associated with estrogen receptor expression in breast cancer. Breast Cancer Res Treat. 134:531–541. 2012. View Article : Google Scholar : PubMed/NCBI
11	Liu M, Chen L, Chan TH, Wang J, Li Y, Li Y, Zeng TT, Yuan YF and Guan XY: Serum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma. Hepatology. 55:1754–1765. 2012. View Article : Google Scholar : PubMed/NCBI
12	Wang Y, Zhou D and Chen S: SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation through activation of p70 S6 kinase and up-regulation of cyclin D1. Mol Endocrinol. 28:935–948. 2014. View Article : Google Scholar : PubMed/NCBI
13	Gatti L, Cossa G, Tinelli S, Carenini N, Arrighetti N, Pennati M, Cominetti D, De Cesare M, Zunino F, Zaffaroni N and Perego P: Improved apoptotic cell death in drug-resistant non-small-cell lung cancer cells by tumor necrosis factor-related apoptosis-inducing ligand-based treatment. J Pharmacol Exp Ther. 348:360–371. 2014. View Article : Google Scholar : PubMed/NCBI
14	Zhang G, Miyake M, Lawton A, Goodison S and Rosser CJ: Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors. BMC Cancer. 14:3102014. View Article : Google Scholar : PubMed/NCBI
15	Virós D, Camacho M, Zarraonandia I, García J, Quer M, Vila L and León X: Prognostic role of MMP-9 expression in head and neck carcinoma patients treated with radiotherapy or chemoradiotherapy. Oral Oncol. 49:322–325. 2013. View Article : Google Scholar : PubMed/NCBI
16	Thorsen SB, Christensen SL, Würtz SO, Lundberg M, Nielsen BS, Vinther L, Knowles M, Gee N, Fredriksson S, Møller S, et al: Plasma levels of the MMP-9: TIMP-1 complex as prognostic biomarker in breast cancer: a retrospective study. BMC Cancer. 13:5982013. View Article : Google Scholar : PubMed/NCBI
17	Wang C, Ma HX, Jin MS, Zou YB, Teng YL, Tian Z, Wang HY, Wang YP and Duan XM: Association of matrix metalloproteinase (MMP)-2 and −9 expression with extra-gastrointestinal stromal tumor metastasis. Asian Pac J Cancer Prev. 15:4187–4192. 2014. View Article : Google Scholar : PubMed/NCBI
18	Yang B, Tang F, Zhang B, Zhao Y, Feng J and Rao Z: Matrix metalloproteinase-9 overexpression is closely related to poor prognosis in patients with colon cancer. World J Surg Oncol. 12:242014. View Article : Google Scholar : PubMed/NCBI
19	Yang YL, Chen CZ, Jin LP, Ji QQ, Chen YZ, Li Q, Zhang XH and Qu JM: Effect and mechanism of the metastasis suppressor gene BRMS1 on the migration of breast cancer cells. Int J Clin Exp Med. 6:908–916. 2013.PubMed/NCBI
20	Wu Y, Jiang W, Wang Y, Wu J, Saiyin H, Qiao X, Mei X, Guo B, Fang X, Zhang L, et al: Breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression. PLoS One. 7:e429762012. View Article : Google Scholar : PubMed/NCBI
21	Ventura BV, Quezada C, Maloney SC, Fernandes BF, Antecka E, Martins C, Bakalian S, di Cesare S and Burnier MN Jr: Expression of the metastasis suppressor BRMS1 in uveal melanoma. Ecancermedicalscience. 8:4102014.PubMed/NCBI
22	Sheng XJ, Zhou YQ, Song QY, Zhou DM and Liu QC: Loss of breast cancer metastasis suppressor 1 promotes ovarian cancer cell metastasis by increasing chemokine receptor 4 expression. Oncol Rep. 27:1011–1018. 2012.PubMed/NCBI