Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1

Zhang,Xiupeng; Jiang,Guiyang; Wu,Jingjing; Zhou,Haijing; Zhang,Yong; Miao,Yuan; Feng,Yangyang; Yu,Juanhan

doi:10.3892/ol.2018.7802

March-2018 Volume 15 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

March-2018 Volume 15 Issue 3

Full Size Image

Article

Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1

Authors:
- Xiupeng Zhang
- Guiyang Jiang
- Jingjing Wu
- Haijing Zhou
- Yong Zhang
- Yuan Miao
- Yangyang Feng
- Juanhan Yu
View Affiliations / Copyright

Affiliations: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Pathology, Cancer Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Pages: 3806-3813
|
Published online on: January 16, 2018

https://doi.org/10.3892/ol.2018.7802
Expand metrics +

Abstract

Zinc finger protein 668 (ZNF668) is a recently discovered protein and its expression levels, as well as its involvement in the invasion and metastasis of non‑small cell lung cancer (NSCLC), are largely unknown. In the present study, immunohistochemical analysis demonstrated that ZNF668 protein expression was decreased in lung tumors (51/167, 30.5%) compared with adjacent normal lung tissues (43/62, 69.4%; P<0.001). Subsequent statistical analysis revealed that ZNF668 expression was negatively associated with increased tumor‑node‑metastasis stage (P=0.019) and lymph node metastasis (P=0.002). Following ZNF668 downregulation by transfection of a ZNF668‑expressing plasmid or small interfering RNA, it was demonstrated that ZNF668 inhibited the invasion and migration of NSCLC cells. Furthermore, restoration of ZNF668 expression downregulated the expression of Snail and increased the protein levels of epithelial (E‑)cadherin and zonula occludens‑1 (ZO‑1). The results of the present study suggest that ZNF668 is downregulated in human NSCLC. Furthermore, restoration of ZNF668 expression was demonstrated to decrease the expression of Snail and increase the expression of E‑cadherin and ZO‑1, suppressing the invasion and migration of NSCLC cells.

View Figures

View References

1	Capaldo CT, Farkas AE and Nusrat A: Epithelial adhesive junctions. F1000Prime Rep. 6:12014. View Article : Google Scholar : PubMed/NCBI
2	Ivanov AI and Naydenov NG: Dynamics and regulation of epithelial adherens junctions: Recent discoveries and controversies. Int Rev Cell Mol Biol. 303:27–99. 2013. View Article : Google Scholar : PubMed/NCBI
3	Brooke MA, Nitoiu D and Kelsell DP: Cell-cell connectivity: Desmosomes and disease. J Pathol. 226:158–71. 2012. View Article : Google Scholar : PubMed/NCBI
4	Liu Y, Xu HT, Dai SD, Wei Q, Yuan XM and Wang EH: Reduction of p120(ctn) isoforms 1 and 3 is significantly associated with metastatic progression of human lung cancer. APMIS. 115:848–562007. View Article : Google Scholar
5	Liu Y, Li QC, Miao Y, Xu HT, Dai SD, Wei Q, Dong QZ, Dong XJ, Zhao Y, Zhao C and Wang EH: Ablation of p120-catenin enhances invasion and metastasis of human lung cancer cells. Cancer Sci. 100:441–448. 2009. View Article : Google Scholar : PubMed/NCBI
6	Liu Y, Wang Y, Zhang Y, Miao Y, Zhao Y, Zhang PX, Jiang GY, Zhang JY, Han Y, Lin XY, et al: Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer. Lung Cancer. 63:375–382. 2009. View Article : Google Scholar : PubMed/NCBI
7	Runkle EA and Mu D: Tight junction proteins: From barrier to tumorigenesis. Cancer Lett. 337:41–48. 2013. View Article : Google Scholar : PubMed/NCBI
8	Balda MS and Matter K: Tight junctions and the regulation of gene expression. Biochim Biophys Acta. 1788:761–767. 2009. View Article : Google Scholar : PubMed/NCBI
9	Hu R, Peng G, Dai H, Breuer EK, Stemke-Hale K, Li K, Gonzalez-Angulo AM, Mills GB and Lin SY: ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer. Cancer Res. 71:6524–6534. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hu R, Wang E, Peng G, Dai H and Lin SY: Zinc finger protein 668 interacts with Tip60 to promote H2AX acetylation after DNA damage. Cell Cycle. 12:2033–41. 2013. View Article : Google Scholar : PubMed/NCBI
11	Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: International Agency for Research on Cancer; 2015
12	Goldstraw P: Updated staging system for lung cancer. Surg Oncol Clin N Am. 20:655–666. 2011. View Article : Google Scholar : PubMed/NCBI
13	Wu Y and Zhou BP: TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. Br J Cancer. 102:639–644. 2010. View Article : Google Scholar : PubMed/NCBI
14	De Craene B, van Roy F and Berx G: Unraveling signalling cascades for the Snail family of transcription factors. Cell Signal. 17:535–547. 2005. View Article : Google Scholar : PubMed/NCBI
15	de Herreros AG, Peiró S, Nassour M and Savagner P: Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J Mammary Gland Biol Neoplasia. 15:135–147. 2010. View Article : Google Scholar : PubMed/NCBI
16	Katoh M and Katoh M: Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades. Cancer Biol Ther. 5:1059–1064. 2006. View Article : Google Scholar : PubMed/NCBI
17	Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, Dargemont C, de Herreros AG, Bellacosa A and Larue L: Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene. 26:7445–7456. 2007. View Article : Google Scholar : PubMed/NCBI
18	Kim SO and Kim MR: [6]-Gingerol prevents disassembly of cell junctions and activities of MMPs in invasive human pancreas cancer cells through ERK/NF-κB/Snail signal transduction pathway. Evid Based Complement Alternat Med. 2013:7618522013. View Article : Google Scholar : PubMed/NCBI
19	Smith BN and Bhowmick NA: Role of EMT in metastasis and therapy resistance. J Clin Med. 5(pii): E172016. View Article : Google Scholar : PubMed/NCBI
20	Lim SO, Kim H and Jung G: p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma. FEBS Lett. 584:2231–2236. 2010. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles