Oncogenic function of p34SEI-1 via NEDD4‑1‑mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway

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

doi:10.3892/ijo.2013.2064

Oncogenic function of p34SEI-1 via NEDD4‑1‑mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway

Authors:
- Samil Jung
- Chengping Li
- Dongjun Jeong
- Soonduck Lee
- Jiyeon Ohk
- Meeyoung Park
- Songyi Han
- Jingjing Duan
- Changjin Kim
- Young Yang
- Keun-Il Kim
- Jong-Seok Lim
- Young-Sook Kang
- Myeong-Sok Lee
View Affiliations

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, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea
Published online on: August 20, 2013 https://doi.org/10.3892/ijo.2013.2064
Pages: 1587-1595

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A 34-KD protein encoded by the SEI-1 gene (p34SEI‑1), is a relatively recently discovered oncoprotein that has multiple important biological functions. Our data show that p34SEI-1 enhances cancer cell survival and promotes tumorigenesis by downregulating the tumor suppressor PTEN, a negative regulator of the PI3K/AKT signaling pathway, and therefore activating the PI3K/AKT signaling pathway. In this process, p34SEI-1 positively affects NEDD4-1 gene expression both at the transcriptional and protein levels. Furthermore, the expression levels of p34SEI-1 and NEDD4-1 were found to be coordinated in tumor tissues obtained from patients with breast cancer. We also show that p34SEI-1 affects the subcellular localization of PTEN.

View Figures

View References

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.	Cortot A, Armand JP and Soria JC: PI3K-AKT-mTOR pathway inhibitors. Bull Cancer. 93:19–26. 2006.(In French).
3.	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 : PubMed/NCBI
4.	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
5.	Yuan TL and Cantley LC: PI3K pathway alterations in cancer: variations on a theme. Oncogene. 27:5497–5510. 2008. View Article : Google Scholar : PubMed/NCBI
6.	Kong D and Yamori T: Advances in development of phosphatidylinositol 3-kinase inhibitors. Curr Med Chem. 16:2839–2854. 2009. View Article : Google Scholar : PubMed/NCBI
7.	Qiao M, Sheng S and Pardee AB: Metastasis and AKT activation. Cell Cycle. 7:2991–2996. 2008. View Article : Google Scholar
8.	Xue G, Restuccia DF, Lan Q, et al: Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-beta signaling axes. Cancer Discov. 2:248–259. 2012. View Article : Google Scholar : PubMed/NCBI
9.	Brader S and Eccles SA: Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori. 90:2–8. 2004.PubMed/NCBI
10.	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
11.	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
12.	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
13.	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
14.	Maehama T and Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 273:13375–13378. 1998. View Article : Google Scholar : PubMed/NCBI
15.	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
16.	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
17.	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 : PubMed/NCBI
18.	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
19.	Tian XX, Pang JC, To SS and Ng HK: Restoration of wild-type PTEN expression leads to apoptosis, induces differentiation, and reduces telomerase activity in human glioma cells. J Neuropathol Exp Neurol. 58:472–479. 1999. View Article : Google Scholar : PubMed/NCBI
20.	McMenamin ME, Soung P, Perera S, Kaplan I, Loda M and Sellers WR: Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 59:4291–4296. 1999.PubMed/NCBI
21.	Chang JG, Chen YJ, Perng LI, et al: Mutation analysis of the PTEN/MMAC1 gene in cancers of the digestive tract. Eur J Cancer. 35:647–651. 1999. View Article : Google Scholar : PubMed/NCBI
22.	Wang X, Trotman LC, Koppie T, et al: NEDD4-1 is a protooncogenic ubiquitin ligase for PTEN. Cell. 128:129–139. 2007. View Article : Google Scholar : PubMed/NCBI
23.	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
24.	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
25.	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
26.	Hong SW, Kim CJ, Park WS, et al: p34SEI-1 inhibits apoptosis through the stabilization of the X-linked inhibitor of apoptosis protein: p34SEI-1 as a novel target for anti-breast cancer strategies. Cancer Res. 69:741–746. 2009. View Article : Google Scholar : PubMed/NCBI
27.	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
28.	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
29.	Lee SL, Hong SW, Shin JS, et al: p34SEI-1 inhibits doxorubicin-induced senescence through a pathway mediated by protein kinase C-delta and c-Jun-NH2-kinase 1 activation in human breast cancer MCF7 cells. Mol Cancer Res. 7:1845–1853. 2009. View Article : Google Scholar : PubMed/NCBI
30.	Lin Q, Wang J, Childress C, Sudol M, Carey DJ and Yang W: HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK. Mol Cell Biol. 30:1541–1554. 2010. View Article : Google Scholar : PubMed/NCBI
31.	Trotman LC, Wang X, Alimonti A, et al: Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell. 128:141–156. 2007. View Article : Google Scholar : PubMed/NCBI
32.	Fouladkou F, Landry T, Kawabe H, et al: The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci USA. 105:8585–8590. 2008. View Article : Google Scholar : PubMed/NCBI
33.	Burow ME, Weldon CB, Melnik LI, et al: PI3-K/AKT regulation of NF-kappaB signaling events in suppression of TNF-induced apoptosis. Biochem Biophys Res Commun. 271:342–345. 2000. View Article : Google Scholar : PubMed/NCBI
34.	Holmes KM, Annala M, Chua CY, et al: Insulin-like growth factor-binding protein 2-driven glioma progression is prevented by blocking a clinically significant integrin, integrin-linked kinase, and NF-kappaB network. Proc Natl Acad Sci USA. 109:3475–3480. 2012. View Article : Google Scholar
35.	Judge AR, Koncarevic A, Hunter RB, Liou HC, Jackman RW and Kandarian SC: Role for IkappaBalpha, but not c-Rel, in skeletal muscle atrophy. Am J Physiol Cell Physiol. 292:C372–C382. 2007. 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.	Sarma SN, Kim YJ and Ryu JC: Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds. Toxicology. 271:122–130. 2010. View Article : Google Scholar : PubMed/NCBI
38.	Du F and Galan JE: Selective inhibition of type III secretion activated signaling by the Salmonella effector AvrA. PLoS Pathog. 5:e10005952009. View Article : Google Scholar : PubMed/NCBI