FBXL20 acts as an invasion inducer and mediates E‑cadherin in colorectal adenocarcinoma

Zhu,Jianjun; Deng,Shishan; Duan,Jie; Xie,Xingguo; Xu,Shiquan; Ran,Maocheng; Dai,Xiaosi; Pu,Yu; Zhang,Xiaoming

doi:10.3892/ol.2014.2031

FBXL20 acts as an invasion inducer and mediates E‑cadherin in colorectal adenocarcinoma

Authors:
- Jianjun Zhu
- Shishan Deng
- Jie Duan
- Xingguo Xie
- Shiquan Xu
- Maocheng Ran
- Xiaosi Dai
- Yu Pu
- Xiaoming Zhang
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Affiliations: Department of Human Anatomy, Premedical College, North Sichuan Medical College, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: April 3, 2014 https://doi.org/10.3892/ol.2014.2031
Pages: 2185-2191

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Abstract

The mechanisms eliciting colorectal adenocarcinoma are not well understood and the FBXL20 gene is problematic as it exhibits an abnormal expression in colorectal cancer cells. In the present study a recombinant plasmid, pReceiver‑M03‑FBL20 expression plasmid was constructed, which overexpressed FBXL20; this was transfected into Lovo cells to form Lovo‑FBL20 cells. The FBXL20 expression level was examined by quantitative polymerase chain reaction (qPCR) and western blot analysis. The cell viability and invasion capacity were measured using cell counting kit 8, Transwell chamber and wound healing assays, respectively. The associated genes, including E‑cadherin, β‑catenin, c‑Myc, SET nuclear oncogene, protein phosphatase‑2A, Axin, p53 and caspase 3, were detected by qPCR and western blotting. It was demonstrated that the FBXL20 expression level was markedly upregulated in the Lovo‑FBL20 cells transfected with pReceiver‑M03‑FBL20 expression plasmid, compared with that of the Lovo cells. In addition, the cell viability and invasion capacity of the Lovo‑FBL20 cells were significantly increased. These increases correlated with a significant upregulation in the expression level of β‑catenin and c‑Myc, and a downregulated expression level of E‑cadherin. The results of the present study indicate that FBXL20 may mediate the ubiquitin degradation of E‑cadherin resulting in an increased invasive ability of malignant cells.

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1	Vonlaufen A, Troillet FX and Armenian B: Screening for colorectal cancer: recommendations. Rev Med Suisse. 9:754–757. 2013.(In French).
2	Du XL, Cai Y and Symanski E: Association between chemotherapy and cognitive impairments in a large cohort of patients with colorectal cancer. Int J Oncol. 42:2123–2133. 2013.PubMed/NCBI
3	George B and Kopetz S: Predictive and prognostic markers in colorectal cancer. Curr Oncol Rep. 13:206–215. 2011. View Article : Google Scholar : PubMed/NCBI
4	Ren F, Sheng WQ and Du X: CD33: a cancer stem cells marker, is used in colorectal cancers. World J Gastroentrol. 19:2603–2611. 2013. View Article : Google Scholar : PubMed/NCBI
5	Smith JC, Brooks L, Hoff PM, et al: KRAS mutations are associated with inferior clinical outcome in patients with metastatic colorectal cancer, but are not predictive for benefit with cediranib. Eur J Cancer. 49:2424–2432. 2013. View Article : Google Scholar : PubMed/NCBI
6	Haugen MH, Johansen HT, Pettersen SJ, et al: Nuclear legumain activity in colorectal cancer. PLoS One. 8:e529802013. View Article : Google Scholar : PubMed/NCBI
7	Welcker M, Larimore EA, Frappier L and Clurman BE: Nucleolar targeting of the fbw7 ubiquitin ligase by a pseudosubstrate and glycogen synthase kinase 3. Mol Cell Biol. 31:1214–1224. 2011. View Article : Google Scholar : PubMed/NCBI
8	Miranda-Carboni GA, Krum SA, Yee K, et al: A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. Genes Dev. 22:3121–3134. 2008. View Article : Google Scholar : PubMed/NCBI
9	Zhu JJ, Li K, Dong L and Chen Y: Role of FBXL20 in human colorectal adenocarcinoma. Oncol Rep. 28:2290–2298. 2012.PubMed/NCBI
10	Amold HK, Zhang X, Daniel CJ, et al: The Axin1 scaffold protein formation of a degradation complex for c-Myc. EMBO J. 28:500–512. 2009. View Article : Google Scholar : PubMed/NCBI
11	Grim JE, Knoblaugh SE, Guthrie KA, et al: Fbw7 and p53 cooperatively suppress advanced and chromosomally unstable intestinal cancer. Mol Cell Biol. 32:2160–2167. 2012. View Article : Google Scholar : PubMed/NCBI
12	Kiatagawa M, Hatakeyama A, Shirane M, et al: An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J. 18:2401–2410. 1999. View Article : Google Scholar : PubMed/NCBI
13	Micel LN, Tentler JJ, Smith PG and Eckhardt GS: Role of ubiquitin ligases and the protesasome in oncogenesis: novel targets for anticancer therapies. J Clin Oncol. 31:1231–1238. 2013. View Article : Google Scholar : PubMed/NCBI
14	Bromberg KD, Kluger HM, Delaunay A, et al: Increased expression of the E3 ubiquitin ligase RNF5 is associated with decreased survival in breast cancer. Cancer Res. 67:8172–8179. 2007. View Article : Google Scholar : PubMed/NCBI
15	Tsai YC, Mendoza A, Mariano JM, et al: The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nat Med. 13:1504–1509. 2007. View Article : Google Scholar : PubMed/NCBI
16	Kioras K, Konstantara A, Kotoula V, et al: The prognostic significance of WNT pathway in surgically-treated colorectal cancer: β-catenin expression predicts for disease-free survival. Anticancer Res. 33:4573–4584. 2013.PubMed/NCBI
17	Freeman TJ, Smith JJ, Chen X, et al: Smad4-mediated signaling inhibits intestinal neoplasia by inhibiting expression of β-catenin. Gastroenterology. 142:562–571. 2012.PubMed/NCBI
18	Kanwar SS, Yu Y, Nautiyal J, et al: The Wnt/beta-catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer. 9:2122010. View Article : Google Scholar : PubMed/NCBI
19	Liu KH, Huynh N, Patel O, et al: P21-activated kinase 1 promotes colorectal cancer survival by up-regulation by hypoxia-inducible factor-1α. Cancer Lett. 340:22–29. 2013.
20	Wu J, Xie N, Xie K, Zeng J, et al: GPR48, a poor prognostic factor, promotes tumor metastatis and activates β-catenin/TCF signaling in colorectal cancer. Carcinogenesis. 34:2861–2869. 2013.PubMed/NCBI
21	Guo S, Xu J, Xue R, et al: Overexpression of A1BI correlates inversely with E-cadherin expression in pancreatic adenocarcinoma and may promote lymph node metastasis. Int J Clin Oncol. March 30–2013.(Epub ahead of print).
22	Oikawa T, Nakamura A, Onishi N, et al: Acquired expression of NFATc1 downregulates E-cadherin and promotes cancer cell invasion. Cancer Res. 73:5100–5109. 2013. View Article : Google Scholar : PubMed/NCBI
23	Huang C: Roles of E3 ubiquitin ligases in cell adhesion and migration. Cell Adh Migr. 4:10–18. 2010. View Article : Google Scholar : PubMed/NCBI
24	Li Q, He Y, Wei L, et al: AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation. Oncogene. 30:1194–1204. 2011. View Article : Google Scholar : PubMed/NCBI
25	Yang LH, Xu HT, Han Y, et al: Axin downregulates TCF-4 transcription via beta-catenin, but not p53, and inhibits the proliferation and invasion of lung cancer cells. Mol Cancer. 9:252010. View Article : Google Scholar : PubMed/NCBI
26	Ikeda S, Kishida M, Matsuura Y, et al: GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin. Oncogene. 19:537–545. 2000. View Article : Google Scholar : PubMed/NCBI
27	Irie A, Harada K, Araki N and Nishimura Y: Phosphorylation of SET protein at Ser171 by protein kinase D2 diminishes its inhibitory effect on protein phosphatase 2A. PloS One. 7:e512422012. View Article : Google Scholar : PubMed/NCBI