ILF2 promotes anchorage independence through direct regulation of PTEN

Li,Na; Liu,Tao; Li,Hui; Zhang,Lifang; Chu,Liping; Meng,Qingge; Qiao,Qinzeng; Han,Weikun; Zhang,Junhui; Guo,Minying; Zhao,Jia

doi:10.3892/ol.2019.10510

ILF2 promotes anchorage independence through direct regulation of PTEN

Authors:
- Na Li
- Tao Liu
- Hui Li
- Lifang Zhang
- Liping Chu
- Qingge Meng
- Qinzeng Qiao
- Weikun Han
- Junhui Zhang
- Minying Guo
- Jia Zhao
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Affiliations: Pathology Department, Xingtai Medical College, Xingtai, Hebei 054000, P.R. China, Department of Internal Medicine, Civil Administration General Hospital of Hebei, Xingtai, Hebei 054000, P.R. China, Department of Internal Medicine, Xingtai Medical College, The Third Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei 054000, P.R. China, Department of Internal Medicine, The Third Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei 054000, P.R. China
Published online on: June 21, 2019 https://doi.org/10.3892/ol.2019.10510
Pages: 1689-1696
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anoikis is a specific form of programmed cell death induced by loss of contact between cells and extracellular matrices or other cells. Only tumor cells that are resistant to anoikis can survive in the state of detachment from the primary tissue during the early stages of metastasis. The ability to resist anoikis is crucial for cancer cell metastasis. ILF2 is a proto‑oncogene previously studied in glioma, NSCLC, esophageal cancer and pancreatic ductal carcinoma. The results from the present study revealed that the transcription factor interleukin enhancer‑binding factor 2 (ILF2) was highly expressed in non‑small cell lung cancer (NSCLC) cell lines compared with in normal cell lines. ChIP and luciferase reporter gene assays demonstrated that ILF2 inhibited the expression level of the tumor suppressor gene phosphatase and tensin homolog (PTEN) by directly binding to its upstream regulatory region. Furthermore, the results from the detection of cell adhesion and apoptosis in cell suspension culture demonstrated that this mechanism enabled NSCLC cells to reduce adherence to the matrix and to survive in this abnormal state. These results suggested that ILF2 may promote the anchorage‑independence of NSCLC cells through the suppression of PTEN.

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1	Fernandez LE, Gabri MR, Guthmann MD, Gomez RE, Gold S, Fainboim L, Gomez DE and Alonso DF: NGcGM3 ganglioside: A privileged target for cancer vaccines. Clin Dev Immunol. 2010:8143972010. View Article : Google Scholar : PubMed/NCBI
2	Ladanyi M and Pao W: Lung adenocarcinoma: Guiding EGFR-targeted therapy and beyond. Mod Pathol. 21 (Suppl 2):S16–S22. 2008. View Article : Google Scholar : PubMed/NCBI
3	Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, Yu LK and Song Y: Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: A systematic review with meta-analysis. J Thorac Oncol. 4:1094–1103. 2009. View Article : Google Scholar : PubMed/NCBI
4	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
5	Wyllie AH: ‘Where, O death, is thy sting?’ A brief review of apoptosis biology. Mol Neurobiol. 42:4–9. 2010. View Article : Google Scholar : PubMed/NCBI
6	Ruoslahti E and Reed JC: Anchorage dependence, integrins, and apoptosis. Cell. 77:477–478. 1994. View Article : Google Scholar : PubMed/NCBI
7	Cheng TL, Symons M and Jou TS: Regulation of anoikis by Cdc42 and Rac1. Exp Cell Res. 295:497–511. 2004. View Article : Google Scholar : PubMed/NCBI
8	Frankel A, Rosen K, Filmus J and Kerbel RS: Induction of anoikis and suppression of human ovarian tumor growth in vivo by down-regulation of Bcl-X(L). Cancer Res. 61:4837–4841. 2001.PubMed/NCBI
9	Yamada KM and Araki M: Tumor suppressor PTEN: Modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 114:2375–2382. 2001.PubMed/NCBI
10	Zhan M, Zhao H and Han ZC: Signalling mechanisms of anoikis. Histol Histopathol. 19:973–983. 2004.PubMed/NCBI
11	Huang Q, He X, Qiu X, Liu X, Sun G, Guo J, Ding Z, Yang L, Ban N, Tao T and Wang D: Expression of NF45 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth. Tumour Biol. 35:10149–10157. 2014. View Article : Google Scholar : PubMed/NCBI
12	Ni T, Mao G, Xue Q, Liu Y, Chen B, Cui X, Lv L, Jia L, Wang Y and Ji L: Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis. J Mol Histol. 46:325–335. 2015. View Article : Google Scholar : PubMed/NCBI
13	Ni S, Zhu J, Zhang J, Zhang S, Li M, Ni R, Liu J, Qiu H, Chen W, Wang H and Guo W: Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC). Tumour Biole. 36:747–756. 2015. View Article : Google Scholar
14	Haselmann V, Kurz A, Bertsch U, Hübner S, Olempska-Müller M, Fritsch J, Häsler R, Pickl A, Fritsche H, Annewanter F, et al: Nuclear death receptor TRAIL-R2 inhibits maturation of let-7 and promotes proliferation of pancreatic and other tumor cells. Gastroenterology. 146:278–290. 2014. View Article : Google Scholar : PubMed/NCBI
15	Wan C, Gong C, Ji L, Liu X, Wang Y, Wang L, Shao M, Yang L, Fan S, Xiao Y, et al: NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma. Mol Cell Biochem. 410:25–35. 2015. View Article : Google Scholar : PubMed/NCBI
16	Lee YY, McKinney KQ, Ghosh S, Iannitti DA, Martinie JB, Caballes FR, Russo MW, Ahrens WA, Lundgren DH, Han DK, et al: Subcellular tissue proteomics of hepatocellular carcinoma for molecular signature discovery. J Proteome Res. 10:5070–5083. 2011. View Article : Google Scholar : PubMed/NCBI
17	Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 275:1943–1947. 1997. View Article : Google Scholar : PubMed/NCBI
18	Datta SR, Brunet A and Greenberg ME: Cellular survival: A play in three Akts. Genes Dev. 13:2905–2927. 1999. View Article : Google Scholar : PubMed/NCBI
19	Sulis ML and Parsons R: PTEN: From pathology to biology. Trends Cell Biol. 13:478–483. 2003. View Article : Google Scholar : PubMed/NCBI
20	Tamura M, Gu J, Matsumoto K, Aota S, Parsons R and Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 280:1614–1617. 1998. View Article : Google Scholar : PubMed/NCBI
21	Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW and Semenza GL: Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: Implications for tumor angiogenesis and therapeutics. Cancer Res. 60:1541–1545. 2000.PubMed/NCBI
22	Li X, Xu Z, Du W, Zhang Z, Wei Y, Wang H, Zhu Z, Qin L, Wang L, Niu Q, et al: Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells. Cancer Cell. 25:575–589. 2014. View Article : Google Scholar : PubMed/NCBI
23	Liu CY, Takemasa A, Liles WC, Goodman RB, Jonas M, Rosen H, Chi E, Winn RK, Harlan JM and Chuang PI: Broad-spectrum caspase inhibition paradoxically augments cell death in TNF-alpha-stimulated neutrophils. Blood. 101:295–304. 2003. View Article : Google Scholar : PubMed/NCBI
24	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
25	Liu Z and Garrard WT: Long-range interactions between three transcriptional enhancers, active Vkappa gene promoters, and a 3′ boundary sequence spanning 46 kilobases. Mol Cell Biol. 25:3220–3231. 2005. View Article : Google Scholar : PubMed/NCBI
26	Győrffy B, Surowiak P, Budczies J and Lánczky A: Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One. 8:e822412013. View Article : Google Scholar : PubMed/NCBI
27	Di Cristofano A and Pandolfi PP: The multiple roles of PTEN in tumor suppression. Cell. 100:387–390. 2000. View Article : Google Scholar : PubMed/NCBI
28	Shi L, Qiu D, Zhao G, Corthesy B, Lees-Miller S, Reeves WH and Kao PN: Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells. Nucleic Acids Res. 35:2302–2310. 2007. View Article : Google Scholar : PubMed/NCBI
29	Reck M, Heigener DF, Mok T, Soria JC and Rabe KF: Management of non-small-cell lung cancer: Recent developments. Lancet. 382:709–719. 2013. View Article : Google Scholar : PubMed/NCBI
30	Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG and Shepherd FA: Non-small-cell lung cancer. Lancet. 378:1727–1740. 2011. View Article : Google Scholar : PubMed/NCBI
31	Tan WL, Jain A, Takano A, Newell EW, Iyer NG, Lim WT, Tan EH, Zhai W, Hillmer AM, Tam WL and Tan DSW: Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. 17:e347–e362. 2016. View Article : Google Scholar : PubMed/NCBI
32	Karmakar S, Mahajan MC, Schulz V, Boyapaty G and Weissman SM: A multiprotein complex necessary for both transcription and DNA replication at the β-globin locus. EMBO J. 29:3260–3271. 2010. View Article : Google Scholar : PubMed/NCBI
33	Shamanna RA, Hoque M, Lewis-Antes A, Azzam EI, Lagunoff D, Pe'ery T and Mathews MB: The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining. Mol Cell Biol. 31:4832–4843. 2011. View Article : Google Scholar : PubMed/NCBI
34	Volk N and Shomron N: Versatility of MicroRNA biogenesis. PLoS One. 6:e193912011. View Article : Google Scholar : PubMed/NCBI
35	Zhao G, Shi L, Qiu D, Hu H and Kao PN: NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function. Exp Cell Res. 305:312–323. 2005. View Article : Google Scholar : PubMed/NCBI
36	Shim C, Zhang W, Rhee CH and Lee JH: Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clin Cancer Res. 4:3045–3050. 1998.PubMed/NCBI
37	Chung FH, Lee HH and Lee HC: ToP: A trend-of-disease- progression procedure works well for identifying cancer genes from multi-state cohort gene expression data for human colorectal cancer. PLoS One. 8:e656832013. View Article : Google Scholar : PubMed/NCBI
38	Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, Cibas ES and Brugge JS: A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 131:966–979. 2007. View Article : Google Scholar : PubMed/NCBI