Distinct regulatory effect of the p34SEI-1 oncoprotein on cancer metastasis in HER2/neu-positive and -negative cells

Jung,Samil; Ohk,Jiyeon; Jeong,Dongjun; Li,Chengping; Lee,Soonduck; Duan,Jingjing; Kim,Changjin; Lim,Jong-Seok; Yang,Young; Kim,Keun-Il; Lee,Myeong-Sok

doi:10.3892/ijo.2014.2403

Distinct regulatory effect of the p34SEI-1 oncoprotein on cancer metastasis in HER2/neu-positive and -negative cells

Authors:
- Samil Jung
- Jiyeon Ohk
- Dongjun Jeong
- Chengping Li
- Soonduck Lee
- Jingjing Duan
- Changjin Kim
- Jong-Seok Lim
- Young Yang
- Keun-Il Kim
- Myeong-Sok Lee
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Affiliations: Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea, Department of Pathology, College of Medicine, Soonchunhyang University, Chonan 330-090, Republic of Korea
Published online on: April 28, 2014 https://doi.org/10.3892/ijo.2014.2403
Pages: 189-196

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Abstract

The p34SEI-1 oncoprotein is involved in a transcriptional regulation, cell cycle regulation, apoptosis, development and many other important cellular functions. Our present study suggests that p34SEI-1 can promote metastasis by enhancing migration and invasion of cancer cells. Consistently, p34SEI-1 expression was found to be increased as the tumor invasiveness progressed in human breast tissues. p34SEI-1 may promote cancer metastasis by activating the PI3K/AKT signaling pathway. In this process, p34SEI-1 activates two different serine/threonine kinases, AKT or ILK, depending on the expression status of HER2/neu oncogene. In HER2/neu suppressed cancer cells, p34SEI-1 promoted metastasis mainly by activating AKT via phosphorylation of the 473 serine residue. In HER2/neu expressing cancer cells, p34SEI-1 overexpression downregulates HER2/neu expression, leading to the activation of another crucial serine/threonine kinase ILK due to phosphorylation of the 178 threonine residue instead of AKT. These results suggest that p34SEI-1 affects cancer metastasis by regulating two different signaling pathways depending on the HER2/neu expression level, in which AKT and ILK modulation can be stimulated by p34SEI-1 overexpression.

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1.	Morgensztern D and McLeod HL: PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs. 16:797–803. 2005. View Article : Google Scholar : PubMed/NCBI
2.	Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS and Workman P: Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol. 8:393–412. 2008. View Article : Google Scholar
3.	LoPiccolo J, Blumenthal GM, Bernstein WB and Dennis PA: Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat. 11:32–50. 2008. View Article : Google Scholar : PubMed/NCBI
4.	Song G, Ouyang G and Bao S: The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 9:59–71. 2005. View Article : Google Scholar : PubMed/NCBI
5.	DeFeo-Jones D, Barnett SF, Fu S, et al: Tumor cell sensitization to apoptotic stimuli by selective inhibition of specific Akt/PKB family members. Mol Cancer Ther. 4:271–279. 2005.PubMed/NCBI
6.	Qiao M, Sheng S and Pardee AB: Metastasis and AKT activation. Cell Cycle. 7:2991–2996. 2008. View Article : Google Scholar
7.	Vivanco I and Sawyers CL: The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2:489–501. 2002. View Article : Google Scholar : PubMed/NCBI
8.	Brader S and Eccles SA: Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori. 90:2–8. 2004.
9.	Stambolic V, Suzuki A, de la Pompa JL, et al: Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 95:29–39. 1998. View Article : Google Scholar : PubMed/NCBI
10.	Akca H, Demiray A, Tokgun O and Yokota J: Invasiveness and anchorage independent growth ability augmented by PTEN inactivation through the PI3K/AKT/NFκB pathway in lung cancer cells. Lung Cancer. 73:302–309. 2011.PubMed/NCBI
11.	Carver BS, Chapinski C, Wongvipat J, et al: Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 19:575–586. 2011. View Article : Google Scholar
12.	Cully M, You H, Levine AJ and Mak TW: Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 6:184–192. 2006. View Article : Google Scholar : PubMed/NCBI
13.	Moasser MM: The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 26:6469–6487. 2007. View Article : Google Scholar : PubMed/NCBI
14.	Baselga J and Swain SM: Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 9:463–475. 2009. View Article : Google Scholar : PubMed/NCBI
15.	Grille SJ, Bellacosa A, Upson J, et al: The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 63:2172–2178. 2003.PubMed/NCBI
16.	Toker A and Yoeli-Lerner M: Akt signaling and cancer: surviving but not moving on. Cancer Res. 66:3963–3966. 2006. View Article : Google Scholar : PubMed/NCBI
17.	Yoeli-Lerner M and Toker A: Akt/PKB signaling in cancer: a function in cell motility and invasion. Cell Cycle. 5:603–605. 2006. View Article : Google Scholar : PubMed/NCBI
18.	Gagnon V, St-Germain ME, Parent S and Asselin E: Akt activity in endometrial cancer cells: Regulation of cell survival through cIAP-1. Int J Oncol. 23:803–810. 2003.PubMed/NCBI
19.	Cross DA, Alessi DR, Cohen P, Andjelkovich M and Hemmings BA: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378:785–789. 1995. View Article : Google Scholar : PubMed/NCBI
20.	Luo J: Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy. Cancer Lett. 273:194–200. 2009. View Article : Google Scholar : PubMed/NCBI
21.	Morin PJ: beta-catenin signaling and cancer. Bioessays. 21:1021–1030. 1999. View Article : Google Scholar
22.	Guturi KK, Mandal T, Chatterjee A, et al: Mechanism of beta-catenin-mediated transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 beta-inactivated prostate cancer cells. J Biol Chem. 287:18287–18296. 2012. View Article : Google Scholar
23.	Hannigan GE, McDonald PC, Walsh MP and Dedhar S: Integrin-linked kinase: not so ‘pseudo’ after all. Oncogene. 30:4375–4385. 2011.
24.	Acconcia F, Barnes CJ, Singh RR, Talukder AH and Kumar R: Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked kinase. Proc Natl Acad Sci USA. 104:6782–6787. 2007. View Article : Google Scholar
25.	Wani AA, Jafarnejad SM, Zhou J and Li G: Integrin-linked kinase regulates melanoma angiogenesis by activating NF-kappaB/interleukin-6 signaling pathway. Oncogene. 30:2778–2788. 2011. View Article : Google Scholar : PubMed/NCBI
26.	Tan C, Cruet-Hennequart S, Troussard A, et al: Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell. 5:79–90. 2004. View Article : Google Scholar : PubMed/NCBI
27.	Taylor CJ, Qiao J, Colon NC, Schlegel C, Josifi E and Chung DH: Integrin-linked kinase regulates phosphatase and tensin homologue activity to promote tumorigenesis in neuroblastoma cells. Surgery. 150:162–168. 2011. View Article : Google Scholar : PubMed/NCBI
28.	Jung S, Li C, Jeong D, et al: Oncogenic function of p34^SEI-1 via NEDD41 mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway. Int J Oncol. 43:1587–1595. 2013.
29.	Wang X, Trotman LC, Koppie T, et al: NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 128:129–139. 2007. View Article : Google Scholar : PubMed/NCBI
30.	Amodio N, Scrima M, Palaia L, et al: Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas. Am J Pathol. 177:2622–2634. 2010. View Article : Google Scholar : PubMed/NCBI
31.	Hayashi R, Goto Y, Ikeda R, Yokoyama KK and Yoshida K: CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation. J Biol Chem. 281:35633–35648. 2006. View Article : Google Scholar
32.	Hsu SI, Yang CM, Sim KG, Hentschel DM, O’Leary E and Bonventre JV: TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1. EMBO J. 20:2273–2285. 2001. View Article : Google Scholar : PubMed/NCBI
33.	Hong SW, Kim CJ, Park WS, et al: p34^SEI-1 inhibits apoptosis through the stabilization of the X-linked inhibitor of apoptosis protein: p34^SEI-1 as a novel target for anti-breast cancer strategies. Cancer Res. 69:741–746. 2009.
34.	Li Y, Nie CJ, Hu L, et al: Characterization of a novel mechanism of genomic instability involving the SEI1/SET/NM23H1 pathway in esophageal cancers. Cancer Res. 70:5695–5705. 2010. View Article : Google Scholar : PubMed/NCBI
35.	Tang DJ, Hu L, Xie D, et al: Oncogenic transformation by SEI-1 is associated with chromosomal instability. Cancer Res. 65:6504–6508. 2005. View Article : Google Scholar : PubMed/NCBI
36.	Van Themsche C, Leblanc V, Parent S and Asselin E: X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem. 284:20462–20466. 2009.PubMed/NCBI
37.	Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T and Altieri DC: IAP regulation of metastasis. Cancer Cell. 17:53–64. 2010. View Article : Google Scholar
38.	Arias AM: Epithelial mesenchymal interactions in cancer and development. Cell. 105:425–431. 2001. View Article : Google Scholar : PubMed/NCBI
39.	Knuefermann C, Lu Y, Liu B, et al: HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene. 22:3205–3212. 2003. View Article : Google Scholar : PubMed/NCBI
40.	Xing X, Wang SC, Xia W, et al: The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis. Nat Med. 6:189–195. 2000. View Article : Google Scholar : PubMed/NCBI
41.	Yuen HF, McCrudden CM, Chan KK, et al: The role of Pea3 group transcription factors in esophageal squamous cell carcinoma. Am J Pathol. 179:992–1003. 2011. View Article : Google Scholar : PubMed/NCBI