Overexpression of fibronectin type III domain containing 3B is correlated with epithelial‑mesenchymal transition and predicts poor prognosis in lung adenocarcinoma

Bian,Tingting; Zheng,Liangfeng; Jiang,Daishan; Liu,Jian; Zhang,Jianguo; Feng,Jia; Zhang,Qing; Qian,Li; Qiu,Hongmei; Liu,Yifei; Yao,Sumei

doi:10.3892/etm.2019.7370

Overexpression of fibronectin type III domain containing 3B is correlated with epithelial‑mesenchymal transition and predicts poor prognosis in lung adenocarcinoma

Authors:
- Tingting Bian
- Liangfeng Zheng
- Daishan Jiang
- Jian Liu
- Jianguo Zhang
- Jia Feng
- Qing Zhang
- Li Qian
- Hongmei Qiu
- Yifei Liu
- Sumei Yao
View Affiliations

Affiliations: Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Central Laboratory, Affiliated Hai'an Hospital of Nantong University, Hai'an, Jiangsu 226600, P.R. China, Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Respiration, Nantong Geriatric Rehabilitation Hospital, Branch of Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Respiratory Medicine, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: March 12, 2019 https://doi.org/10.3892/etm.2019.7370
Pages: 3317-3326
Copyright: © Bian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Fibronectin (FN) type III domain containing 3B (FNDC3B), a member of the FN family, regulates the invasion and metastasis of cells in numerous tumor types. However, the mechanisms through which FNDC3B regulates carcinogenesis in lung adenocarcinoma (LADC) tissues have remained elusive. The present study revealed that the protein levels of FNDC3B and vimentin were significantly elevated in LADC tissues compared with those in normal lung tissues. By contrast, the expression of E‑cadherin was decreased in LADC tissues compared with that in normal lung tissues. Furthermore, the aberrant expression of FNDC3B and epithelial‑mesenchymal transition (EMT) markers was significantly associated with histological differentiation, lymph node metastasis and tumor‑nodes‑metastasis stage. Kaplan‑Meier analysis indicated that a high expression of FNDC3B may be associated with poor overall survival of patients with LADC. In addition, overexpression of FNDC3B promoted the protein expression of EMT‑associated genes in the A549 lung adenocarcinoma cell line. In conclusion, the present results support the notion that FNDC3B acts as an oncogene in LADC; it may serve a pivotal role in the development and progression of LADC and may participate in the regulation of the EMT.

View Figures

View References

1	Cha MJ, Lee HY, Lee KS, Jeong JY, Han J, Shim YM and Hwang HS: Micropapillary and solid subtypes of invasive lung adenocarcinoma: Clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg. 147:921–928.e2. 2014. View Article : Google Scholar : PubMed/NCBI
2	Ujiie H, Kadota K, Chaft JE, Buitrago D, Sima CS, Lee MC, Huang J, Travis WD, Rizk NP, Rudin CM, et al: Solid predominant histologic subtype in resected stage I lung adenocarcinoma is an independent predictor of early, extrathoracic, multisite recurrence and of poor postrecurrence survival. J Clin Oncol. 33:2877–2884. 2015. View Article : Google Scholar : PubMed/NCBI
3	Xu S, Xi J, Jiang W, Lu S and Wang Q: Solid Component and Tumor Size Correlate With Prognosis of Stage IB Lung Adenocarcinoma. Ann Thorac Surg. 99:961–967. 2015. View Article : Google Scholar : PubMed/NCBI
4	Yang X, Liu Y, Lian F, Guo L, Wen P, Liu XY and Lin DM: Lepidic and micropapillary growth pattern and expression of Napsin A can stratify patients of stage I lung adenocarcinoma into different prognostic subgroup. Int J Clin Exp Pathol. 7:1459–1468. 2014.PubMed/NCBI
5	Zhang Y, Wang R, Cai D, Li Y, Pan Y, Hu H, Wang L, Li H, Ye T, Luo X, et al: A comprehensive investigation of molecular features and prognosis of lung adenocarcinoma with micropapillary component. J Thorac Oncol. 9:1772–1778. 2014. View Article : Google Scholar : PubMed/NCBI
6	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 1:10–29. 2012. View Article : Google Scholar
7	Lortettieulent J, Soerjomataram I, Ferlay J, Rutherford M, Weiderpass E and Bray F: International trends in lung cancer incidence by histological subtype: adenocarcinoma stabilizing in men but still increasing in women. Lung Cancer. 84:13–22. 2014. View Article : Google Scholar : PubMed/NCBI
8	Smith CB, Kelley AS and Meier DE: Evidence for new standard of care in non-small cell lung cancer patients. Semin Thorac Cardiovasc Surg. 22:193–194. 2011. View Article : Google Scholar
9	Kishimoto K, Nishizuka M, Ueda T, Kajita K, Ugawa S, Shimada S, Osada S and Imagawa M: Indispensable role of factor for adipocyte differentiation 104 (fad104) in lung maturation. Exp Cell Res. 317:2110–2123. 2011. View Article : Google Scholar : PubMed/NCBI
10	Tominaga K, Kondo C, Johmura Y, Nishizuka M and Imagawa M: The novel gene fad104, containing a fibronectin type III domain, has a significant role in adipogenesis. FEBS Lett. 577:49–54. 2004. View Article : Google Scholar : PubMed/NCBI
11	Nishizuka M, Kishimoto K, Kato A, Ikawa M, Okabe M, Sato R, Niida H, Nakanishi M, Osada S and Imagawa M: Disruption of the novel gene fad104 causes rapid postnatal death and attenuation of cell proliferation, adhesion, spreading and migration. Exp Cell Res. 315:809–819. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kishimoto K, Kato AS, Nishizuka M and Imagawa M: Fad104, a positive regulator of adipogenesis, negatively regulates osteoblast differentiation. Biochem Biophys Res Commun. 397:187–191. 2010. View Article : Google Scholar : PubMed/NCBI
13	Lin F, Ren XD, Pan Z, Macri L, Zong WX, Tonnesen MG, Rafailovich M, Bar-Sagi D and Clark RA: Fibronectin growth factor-binding domains are required for fibroblast survival. J Invest Dermatol. 131:84–98. 2011. View Article : Google Scholar : PubMed/NCBI
14	Obara M, Sakuma T and Fujikawa K: The third type III module of human fibronectin mediates cell adhesion and migration. J Biochem. 147:327–335. 2010. View Article : Google Scholar : PubMed/NCBI
15	Lin CH, Lin YW, Chen YC, Liao CC, Jou YS, Hsu MT and Chen CF: FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma. Oncotarget. 7:49498–49508. 2016.PubMed/NCBI
16	Sung WJ, Kim H and Park KK: The biological role of epithelial-mesenchymal transition in lung cancer (Review). Oncol Rep. 36:1199–1206. 2016. View Article : Google Scholar : PubMed/NCBI
17	Weber CE, Li NY, Wai PY and Kuo PC: Epithelial-mesenchymal transition, TGF-Î2, and osteopontin in wound healing and tissue remodeling after injury. J Burn Care Res. 33:311–318-. 2012. View Article : Google Scholar : PubMed/NCBI
18	Geiger TR and Peeper DS: Metastasis mechanisms. Biochim Biophys Acta. 1796:293–308. 2009.PubMed/NCBI
19	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428-. 2015. View Article : Google Scholar
20	Cai C, Rajaram M, Zhou X, Liu Q, Marchica J, Li J and Powers RS: Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene FNDC3B. Cell Cycle. 11:1773–1781. 2012. View Article : Google Scholar : PubMed/NCBI
21	Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V, et al: The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 11:39–51. 2016. View Article : Google Scholar : PubMed/NCBI
22	Sabattini E, Bisgaard K, Ascani S, Poggi S, Piccioli M, Ceccarelli C, Pieri F, Fraternali-Orcioni G and Pileri SA: The EnVision++ system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques. J Clin Pathol. 51:506–511. 1998. View Article : Google Scholar : PubMed/NCBI
23	Cui Y, Liu J, Yin HB, Liu YF and Liu JH: Fibulin-1 functions as a prognostic factor in lung adenocarcinoma. Jpn J Clin Oncol. 45:854–859. 2015. View Article : Google Scholar : PubMed/NCBI
24	Liu Y, Gai L, Liu J, Cui Y, Zhang Y and Feng J: Expression of poly(C)-binding protein 1 (PCBP1) in NSCLC as a negative regulator of EMT and its clinical value. Int J Clin Exp Pathol. 8:7165–7172. 2015.PubMed/NCBI
25	Brzozowska A, Sodolski T, Duma D, Mazurkiewicz T and Mazurkiewicz M: Evaluation of prognostic parameters of E-cadherin status in breast cancer treatment. Ann Agric Environ Med. 19:541–546. 2012.PubMed/NCBI
26	Xu B, Jin DY, Lou WH and Wang DS: Lipocalin-2 is associated with a good prognosis and reversing epithelial-to-mesenchymal transition in pancreatic cancer. World J Surg. 37:1892–1900. 2013. View Article : Google Scholar : PubMed/NCBI
27	Xu MM, Mao GX, Liu J, Li JC, Huang H, Liu YF and Liu JH: Low expression of the FoxO4 gene may contribute to the phenomenon of EMT in non-small cell lung cancer. Asian Pac J Cancer Prev. 15:4013–4018-. 2014. View Article : Google Scholar : PubMed/NCBI
28	Bian T, Jiang D, Liu J, Yuan X, Feng J, Li Q, Zhang Q, Li X, Liu Y and Zhang J: miR-1236-3p suppresses the migration and invasion by targeting KLF8 in lung adenocarcinoma A549 cells. Biochem Biophys Res Commun. 492:461–467. 2017. View Article : Google Scholar : PubMed/NCBI
29	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
30	Chen CF, Hsu EC, Lin KT, Tu PH, Chang HW, Lin CH, Chen YJ, Gu DL, Lin CH, Wu JY, et al: Overlapping high-resolution copy number alterations in cancer genomes identified putative cancer genes in hepatocellular carcinoma. Hepatology. 52:1690–1701. 2010. View Article : Google Scholar : PubMed/NCBI
31	Fan X, Xu C, Deng W, Zhong G, Cai Q and Lin T: Upregulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression. BMC Cancer. 13:612013. View Article : Google Scholar : PubMed/NCBI
32	Shan ZZ, Yan XB, Yan LL, Tian Y, Meng QC, Qiu WW, Zhang Z and Jin ZM: Overexpression of Tbx3 is correlated with Epithelial-Mesenchymal Transition phenotype and predicts poor prognosis of colorectal cancer. Am J Cancer Res. 5:344–353. 2015.PubMed/NCBI
33	Koren A, Motaln H and Cufer T: Lung cancer stem cells: a biological and clinical perspective. Cell Oncol (Dordr). 36:265–275. 2013. View Article : Google Scholar : PubMed/NCBI
34	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial\|[ndash]\|mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
35	Shi Y, Wu H, Zhang M, Lei D, Meng F and Fan X: Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagnostic Pathology. 8:89. 2013. View Article : Google Scholar : PubMed/NCBI
36	Goto M, Osada S, Imagawa M and Nishizuka M: FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-β mediated EMT in cervical cancer cells. Sci Rep. 7:163652017. View Article : Google Scholar : PubMed/NCBI