Tumor necrosis factor receptor 2 promotes growth of colorectal cancer via the PI3K/AKT signaling pathway

Zhao,Tao; Li,Huihui; Liu,Zifeng

doi:10.3892/ol.2016.5403

Tumor necrosis factor receptor 2 promotes growth of colorectal cancer via the PI3K/AKT signaling pathway

Authors:
- Tao Zhao
- Huihui Li
- Zifeng Liu
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Affiliations: Oncology Department, Second People's Hospital of Dongying City, Dongying, Shandong 257335, P.R. China, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250017, P.R. China, Second Department of Liver Failure, 302 Hospital of PLA, Beijing 100000, P.R. China
Published online on: November 21, 2016 https://doi.org/10.3892/ol.2016.5403
Pages: 342-346

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Abstract

Tumor necrosis factor receptor 2 (TNFR2) is the receptor for tumor necrosis factor α (TNF-α). TNFR2 differs from tumor necrosis factor 1 (TNFR1) in various ways and is mainly expressed in hematopoietic and endothelial cells. However, studies about its functions in tumors are limited. The contributions of TNFR2 in colorectal cancer (CRC) remain unknown. In the present study, it was found that TNFR2 was positively associated with Ki67 expression in CRC tissues using immunohistochemistry (IHC), and western blot analysis found that Ki67 was upregulated by overexpressing TNFR2 in SW1116 cells and inhibited by silencing TNFR2 in HT29 cells. Methyl thiazolyl tetrazolium assay found that growth of SW1116 cells overexpressing TNFR2 was significantly increased compared with the control group and that the growth of HT29 cells subsequent to silencing TNFR2 was significantly decreased compared with the control group. Clone formation assay found that more clones were formed in SW1116 cells overexpressing TNFR2 than the control group, and less clones formed in HT29 cells subsequent to silencing TNFR2 than the control group. In addition, western blot analysis found that phosphorylation of protein kinase B (AKT) was activated subsequent to overexpressing TNFR2 in SW1116 cells, and inhibited following silencing of TNFR2 in HT29 cells. Additionally, treatment using LY294002 significantly abrogated the promotion of Ki67 expression, growth and clone formation abilities induced by TNFR2 overexpression in SW1116 cells. All the results suggest that TNFR2 can significantly promote CRC growth via the phosphoinositide 3-kinase/AKT signaling pathway; this provides evidential support for taking TNFR2 as a new target for CRC treatment.

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1	Becker C, Fantini MC, Wirtz S, Nikolaev A, Lehr HA, Galle PR, Rose-John S and Neurath MF: IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle. 4:217–220. 2005. View Article : Google Scholar : PubMed/NCBI
2	Smith AR, Marquez RT, Tsao WC, Pathak S, Roy A, Ping J, Wilkerson B, Lan L, Meng W, Neufeld KL, et al: Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression. Oncotarget. 6:12558–12573. 2015. View Article : Google Scholar : PubMed/NCBI
3	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
4	National Research Council (US) Committee on A Framwework for Developing a New Taxonomy of Disease, . Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. National Academies Press (US); Washington (DC): 2011
5	Mirnezami R, Nicholson J and Darzi A: Preparing for precision medicine. N Engl J Med. 366:489–491. 2012. View Article : Google Scholar : PubMed/NCBI
6	Hosono K, Yamada E, Endo H, Takahashi H, Inamori M, Hippo Y, Nakagama H and Nakajima A: Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas. World J Gastroenterol. 18:5360–5368. 2012. View Article : Google Scholar : PubMed/NCBI
7	Seitz C, Muller P, Krieg RC, Mannel DN and Hehlgans T: A novel p75TNF receptor isoform mediating NFkappa B activation. J Biol Chem. 276:19390–19395. 2001. View Article : Google Scholar : PubMed/NCBI
8	Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, et al: The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 332:478–484. 2011. View Article : Google Scholar : PubMed/NCBI
9	Guo Z, Li Q, Han Y, Liang Y, Xu Z and Ren T: Prevention of LPS-induced acute lung injury in mice by progranulin. Mediators Inflamm. 2012:5407942012. View Article : Google Scholar : PubMed/NCBI
10	Zhao YP, Tian QY, Frenkel S and Liu CJ: The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials. 34:6412–6421. 2013. View Article : Google Scholar : PubMed/NCBI
11	Tanimura Y, Kokuryo T, Tsunoda N, Yamazaki Y, Oda K, Nimura Y, Mon N Naing, Huang P, Nakanuma Y, Chen MF, et al: Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2. Cancer Lett. 219:205–213. 2005. View Article : Google Scholar : PubMed/NCBI
12	Szlosarek PW and Balkwill FR: Tumour necrosis factor alpha: A potential target for the therapy of solid tumours. Lancet Oncol. 4:565–573. 2003. View Article : Google Scholar : PubMed/NCBI
13	Jöhrer K, Janke K, Krugmann J, Fiegl M and Greil R: Transendothelial migration of myeloma cells is increased by tumor necrosis factor (TNF)-alpha via TNF Receptor 2 and autocrine Up-regulation of MCP-1. Clin Cancer Res. 10:1901–1910. 2004. View Article : Google Scholar : PubMed/NCBI
14	Arnott CH, Scott KA, Moore RJ, Robinson SC, Thompson RG and Balkwill FR: Expression of both TNF-alpha receptor subtypes is essential for optimal skin tumour development. Oncogene. 23:1902–1910. 2004. View Article : Google Scholar : PubMed/NCBI
15	Baud V and Karin M: Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 11:372–377. 2001. View Article : Google Scholar : PubMed/NCBI
16	Grell M, Zimmermann G, Hülser D, Pfizenmaier K and Scheurich P: TNF receptors TR60 and TR80 can mediate apoptosis via induction of distinct signal pathways. J Immunol. 153:1963–1972. 1994.PubMed/NCBI
17	Dahlmann M, Okhrimenko A, Marcinkowski P, Osterland M, Herrmann P, Smith J, Heizmann CW, Schlag PM and Stein U: RAGE mediates S100A4-induced cell motility via MAPK/ERK and hypoxia signaling and is a prognostic biomarker for human colorectal cancer metastasis. Oncotarget. 5:3220–3233. 2014. View Article : Google Scholar : PubMed/NCBI
18	Hu SY, Tai CC, Li YH and Wu JL: Progranulin compensates for blocked IGF-1 signaling to promote myotube hypertrophy in C2C12 myoblasts via the PI3K/Akt/mTOR pathway. FEBS Lett. 586:3485–3492. 2012. View Article : Google Scholar : PubMed/NCBI
19	Bai T, Lian LH, Wu YL, Wan Y and Nan JX: Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells. Int Immunopharmacol. 15:275–281. 2013. View Article : Google Scholar : PubMed/NCBI
20	Li N, Cui J, Duan X, Chen H and Fan F: Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway in human Tenon's fibroblasts. Invest Ophthalmol Vis Sci. 53:1670–1678. 2012. View Article : Google Scholar : PubMed/NCBI
21	Miao B and Degterev A: Targeting phospshatidylinositol 3-kinase signaling with novel phosphatidylinositol 3,4,5-triphosphate antagonists. Autophagy. 7:650–651. 2011. View Article : Google Scholar : PubMed/NCBI
22	Gentilini A, Marra F, Gentilini P and Pinzani M: Phosphatidylinositol-3 kinase and extracellular signal-regulated kinase mediate the chemotactic and mitogenic effects of insulin-like growth factor-I in human hepatic stellate cells. J Hepatol. 32:227–234. 2000. View Article : Google Scholar : PubMed/NCBI