SATB1 protein is associated with the epithelial‑mesenchymal transition process in non‑small cell lung cancers

Glatzel‑Plucinska,Natalia; Piotrowska,Aleksandra; Rzechonek,Adam; Podhorska‑Okolow,Marzenna; Dziegiel,Piotr

doi:10.3892/or.2021.8069

SATB1 protein is associated with the epithelial‑mesenchymal transition process in non‑small cell lung cancers

Authors:
- Natalia Glatzel‑Plucinska
- Aleksandra Piotrowska
- Adam Rzechonek
- Marzenna Podhorska‑Okolow
- Piotr Dziegiel
View Affiliations

Affiliations: Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50‑368 Wroclaw, Poland, Department of Thoracic Surgery, Wroclaw Medical University, 53‑439 Wroclaw, Poland, Department of Ultrastructural Research, Wroclaw Medical University, 50‑368 Wroclaw, Poland
Published online on: April 28, 2021 https://doi.org/10.3892/or.2021.8069
Article Number: 118
Copyright: © Glatzel‑Plucinska 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

Lung cancer is one of the most frequently diagnosed neoplasms and the leading cause of cancer‑related mortality worldwide. Its predominant subtype is non‑small cell lung cancer (NSCLC), which accounts for over 80% of the cases. Surprisingly, the majority of lung cancer‑related deaths are caused not by a primary tumour itself, but by its metastasis to distant organs. Therefore, it becomes especially important to identify the factors involved in lung cancer metastatic spread. Special AT‑rich binding protein 1 (SATB1) is a nuclear matrix protein that mediates chromatin looping and plays the role of global transcriptional regulator. During the past decade, it has received much attention as a factor promoting tumour invasion. In breast, colorectal and prostate cancers, SATB1 has been shown to influence the epithelial‑mesenchymal transition (EMT) process, which is thought to be crucial for cancer metastasis. The aim of this study was to analyse the possible correlations between the expression of SATB1 and major EMT‑associated proteins in NSCLC clinical samples. Additionally, the impact of EMT induction in NSCLC cell lines on SATB1 mRNA expression was also investigated. Immunohistochemistry was used to assess the expression of SATB1, SNAIL, SLUG, Twist1, E‑cadherin, and N‑cadherin in 242 lung cancer clinical samples. EMT was induced by TGF‑β1 treatment in the A549 and NCI‑H1703 lung cancer cell lines. Changes in gene expression profiles were analyzed using real‑time PCR and Droplet Digital PCR. SATB1 expression was positively correlated with the expression of SNAIL (R=0.129; P=0.045), SLUG (R=0.449; P<0.0001), and Twist1 (R=0.264; P<0.0001). Moreover, SATB1 expression significantly increased after in vitro EMT induction in A549 and NCI‑H1703 cell lines. The results obtained may point to the role of SATB1 as one of the regulators of EMT in NSCLC.

View Figures

View References

1	Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I and Bray F: Global Cancer Observatory: Cancer Today. Int Agency Res Cancer. 2018 https://publications.iarc.fr/Databases/Iarc-Cancerbases/Cancer-Today-Powered-By-GLOBOCAN-2018--2018December 62019 12 06;
2	Zappa C and Mousa SA: Non-small cell lung cancer: Current treatment and future advances. Transl Lung Cancer Res. 5:288–300. 2016. View Article : Google Scholar : PubMed/NCBI
3	Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: Introduction to The 2015 World Health Organization Classification of tumours of the lung, pleura, thymus and heart. J Thorac Oncol. 10:1240–1242. 2015. View Article : Google Scholar : PubMed/NCBI
4	Perlikos F, Harrington KJ and Syrigos KN: Key molecular mechanisms in lung cancer invasion and metastasis: A comprehensive review. Crit Rev Oncol Hematol. 87:1–11. 2013. View Article : Google Scholar : PubMed/NCBI
5	Tamura T, Kurishima K, Nakazawa K, Kagahashi K, Ishikawa H, Satoh H and Hizawa N: Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol. 3:217–221. 2015. View Article : Google Scholar : PubMed/NCBI
6	Milovanovic IS, Stjepanovic M and Mitrovic D: Distribution patterns of the metastases of the lung carcinoma in relation to histological type of the primary tumor: An autopsy study. Ann Thorac Med. 12:191–198. 2017. View Article : Google Scholar : PubMed/NCBI
7	Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T and Ho C: Patterns of spread and prognostic implications of lung cancer metastasis in an era of driver mutations. Curr Oncol. 24:228–233. 2017. View Article : Google Scholar : PubMed/NCBI
8	Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, et al: SEER Cancer Statistics Review, 1975–2017. https://seer.cancer.gov/csr/1975_2017April 15–2020
9	Diepenbruck M and Christofori G: Epithelial-mesenchymal transition (EMT) and metastasis: Yes, no, maybe? Curr Opin Cell Biol. 43:7–13. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yang X, Liang X, Zheng M and Tang Y: Cellular phenotype plasticity in cancer dormancy and metastasis. Front Oncol. 8:5052018. View Article : Google Scholar : PubMed/NCBI
11	De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI
12	Zhang Y and Weinberg RA: Epithelial-to-mesenchymal transition in cancer: Complexity and opportunities. Front Med. 12:361–373. 2018. View Article : Google Scholar : PubMed/NCBI
13	Santamaria PG, Moreno-Bueno G, Portillo F and Cano A: EMT: Present and future in clinical oncology. Mol Oncol. 11:718–738. 2017. View Article : Google Scholar : PubMed/NCBI
14	Singh M, Yelle N, Venugopal C and Singh SK: EMT: Mechanisms and therapeutic implications. Pharmacol Ther. 182:80–94. 2018. View Article : Google Scholar : PubMed/NCBI
15	Pastushenko I and Blanpain C: EMT transition states during tumor progression and metastasis. Trends Cell Biol. 29:212–226. 2019. View Article : Google Scholar : PubMed/NCBI
16	Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Löchner D and Birchmeier W: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 113:173–185. 1991. View Article : Google Scholar : PubMed/NCBI
17	Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI
18	Nagathihalli NS, Massion PP, Gonzalez AL, Lu P and Datta PK: Smoking induces epithelial-to-mesenchymal transition in non-small cell lung cancer through HDAC-mediated downregulation of E-cadherin. Mol Cancer Ther. 11:2362–2372. 2012. View Article : Google Scholar : PubMed/NCBI
19	Mahmood MQ, Walters EH, Shukla SD, Weston S, Muller HK, Ward C and Sohal SS: β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction. Sci Rep. 7:108322017. View Article : Google Scholar : PubMed/NCBI
20	Zhu X, Chen L, Liu L and Niu X: EMT-Mediated Acquired EGFR-TKI resistance in NSCLC: Mechanisms and strategies. Front Oncol. 9:10442019. View Article : Google Scholar : PubMed/NCBI
21	Tulchinsky E, Demidov O, Kriajevska M, Barlev NA and Imyanitov E: EMT: A mechanism for escape from EGFR-targeted therapy in lung cancer. Biochim Biophys Acta Rev Cancer. 1871:29–39. 2019. View Article : Google Scholar : PubMed/NCBI
22	Bronte G, Bravaccini S, Bronte E, Burgio MA, Rolfo C, Delmonte A and Crinò L: Epithelial-to-mesenchymal transition in the context of epidermal growth factor receptor inhibition in non-small-cell lung cancer. Biol Rev Camb Philos Soc. 93:1735–1746. 2018. View Article : Google Scholar : PubMed/NCBI
23	Li M, Yang J, Zhou W, Ren Y, Wang X, Chen H, Zhang J, Chen J, Sun Y, Cui L, et al: Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer. Br J Cancer. 117:974–983. 2017. View Article : Google Scholar : PubMed/NCBI
24	Santamaría PG, Moreno-Bueno G and Cano A: Contribution of epithelial plasticity to therapy resistance. J Clin Med. 8:6762019. View Article : Google Scholar
25	Liang SQ, Marti TM, Dorn P, Froment L, Hall SR, Berezowska S, Kocher G, Schmid RA and Peng RW: Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer. Cell Death Dis. 6:e18242015. View Article : Google Scholar : PubMed/NCBI
26	Zheng HC: The molecular mechanisms of chemoresistance in cancers. Oncotarget. 8:59950–59964. 2017. View Article : Google Scholar : PubMed/NCBI
27	Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, et al: Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 527:472–476. 2015. View Article : Google Scholar : PubMed/NCBI
28	Kohwi-Shigematsu T, Kohwi Y, Takahashi K, Richards HW, Ayers SD, Han HJ and Cai S: SATB1-mediated functional packaging of chromatin into loops. Methods. 58:243–254. 2012. View Article : Google Scholar : PubMed/NCBI
29	Galande S, Purbey PK, Notani D and Kumar PP: The third dimension of gene regulation: Organization of dynamic chromatin loopscape by SATB1. Curr Opin Genet Dev. 17:408–414. 2007. View Article : Google Scholar : PubMed/NCBI
30	Kohwi-Shigematsu T, Poterlowicz K, Ordinario E, Han HJ, Botchkarev VA and Kohwi Y: Genome organizing function of SATB1 in tumor progression. Semin Cancer Biol. 23:72–79. 2013. View Article : Google Scholar : PubMed/NCBI
31	Fessing MY, Mardaryev AN, Gdula MR, Sharov AA, Sharova TY, Rapisarda V, Gordon KB, Smorodchenko AD, Poterlowicz K, Ferone G, et al: p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis. J Cell Biol. 194:825–839. 2011. View Article : Google Scholar : PubMed/NCBI
32	Pavan Kumar P, Purbey PK, Sinha CK, Notani D, Limaye A, Jayani RS and Galande S: Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. Mol Cell. 22:231–243. 2006. View Article : Google Scholar : PubMed/NCBI
33	Purbey PK, Singh S, Notani D, Kumar PP, Limaye AS and Galande S: Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1. Mol Cell Biol. 29:1321–1337. 2009. View Article : Google Scholar : PubMed/NCBI
34	Nagpal N, Ahmad HM, Molparia B and Kulshreshtha R: MicroRNA-191, an estrogen-responsive microRNA, functions as an oncogenic regulator in human breast cancer. Carcinogenesis. 34:1889–1899. 2013. View Article : Google Scholar : PubMed/NCBI
35	Brown CY, Dayan S, Wong SW, Kaczmarek A, Hope CM, Pederson SM, Arnet V, Goodall GJ, Russell D, Sadlon TJ and Barry SC: FOXP3 and miR-155 cooperate to control the invasive potential of human breast cancer cells by down regulating ZEB2 independently of ZEB1. Oncotarget. 9:27708–27727. 2018. View Article : Google Scholar : PubMed/NCBI
36	Li QQ, Chen ZQ, Cao XX, Xu JD, Xu JW, Chen YY, Wang WJ, Chen Q, Tang F, Liu XP and Xu ZD: Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial-mesenchymal transition of breast cancer cells. Cell Death Differ. 18:16–25. 2011. View Article : Google Scholar : PubMed/NCBI
37	McInnes N, Sadlon TJ, Brown CY, Pederson S, Beyer M, Schultze JL, McColl S, Goodall GJ and Barry SC: FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells. Oncogene. 31:1045–1054. 2012. View Article : Google Scholar : PubMed/NCBI
38	Pan X, Li D, Huo J, Kong F, Yang H and Ma X: LINC01016 promotes the malignant phenotype of endometrial cancer cells by regulating the miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis. Cell Death Dis. 9:3032018. View Article : Google Scholar : PubMed/NCBI
39	Lopes-Ramos CM, Habr-Gama A, Quevedo Bde S, Felício NM, Bettoni F, Koyama FC, Asprino PF, Galante PA, Gama-Rodrigues J, Camargo AA, et al: Overexpression of miR-21-5p as a predictive marker for complete tumor regression to neoadjuvant chemoradiotherapy in rectal cancer patients. BMC Med Genomics. 7:682014. View Article : Google Scholar : PubMed/NCBI
40	Kowalczyk AE, Krazinski BE, Godlewski J, Grzegrzolka J, Kiewisz J, Kwiatkowski P, Sliwinska-Jewsiewicka A, Dziegiel P and Kmiec Z: SATB1 is Down-regulated in clear cell renal cell carcinoma and correlates with miR-21-5p overexpression and poor prognosis. Cancer Genomics Proteomics. 13:209–217. 2016.PubMed/NCBI
41	Alvarez JD, Yasui DH, Niida H, Joh T, Loh DY and Kohwi-Shigematsu T: The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 14:521–535. 2000.PubMed/NCBI
42	Savarese F, Dávila A, Nechanitzky R, De La Rosa-Velazquez I, Pereira CF, Engelke R, Takahashi K, Jenuwein T, Kohwi-Shigematsu T, Fisher AG and Grosschedl R: Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression. Genes Dev. 23:2625–2638. 2009. View Article : Google Scholar : PubMed/NCBI
43	Han HJ, Russo J, Kohwi Y and Kohwi-Shigematsu T: SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature. 452:187–193. 2008. View Article : Google Scholar : PubMed/NCBI
44	Nodin B, Johannesson H, Wangefjord S, O'Connor DP, Lindquist KE, Uhlén M, Jirström K and Eberhard J: Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer. Diagn Pathol. 7:1152012. View Article : Google Scholar : PubMed/NCBI
45	Shukla S, Sharma H, Abbas A, MacLennan GT, Fu P, Danielpour D and Gupta S: Upregulation of SATB1 is associated with prostate cancer aggressiveness and disease progression. PLoS One. 8:e535272013. View Article : Google Scholar : PubMed/NCBI
46	Tu W, Luo M, Wang Z, Yan W, Xia Y, Deng H, He J, Han P and Tian D: Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer. Liver Int. 32:1064–1078. 2012. View Article : Google Scholar : PubMed/NCBI
47	Han B, Luan L, Xu Z and Wu B: Expression and biological roles of SATB1 in human bladder cancer. Tumor Biol. 34:2943–2949. 2013. View Article : Google Scholar : PubMed/NCBI
48	Nodin B, Hedner C, Uhlén M and Jirström K: Expression of the global regulator SATB1 is an independent factor of poor prognosis in high grade epithelial ovarian cancer. J Ovarian Res. 5:242012. View Article : Google Scholar : PubMed/NCBI
49	Wang S, Zeng J, Xiao R, Xu G, Liu G, Xiong D, Ye Y, Chen B, Wang H, Luo Q and Huang Z: Poor prognosis and SATB1 overexpression in solid tumors: A meta-analysis. Cancer Manag Res. 10:1471–1478. 2018. View Article : Google Scholar : PubMed/NCBI
50	Sun Z, Zhang C, Zou X, Jiang G, Xu Z, Li W and Xie H: Special AT-rich sequence-binding protein-1 participates in the maintenance of breast cancer stem cells through regulation of the Notch signaling pathway and expression of Snail1 and Twist1. Mol Med Rep. 11:3235–3242. 2015. View Article : Google Scholar : PubMed/NCBI
51	Lv JH, Wang F, Shen MH, Wang X and Zhou XJ: SATB1 expression is correlated with β-catenin associated epithelial-mesenchymal transition in colorectal cancer. Cancer Biol Ther. 17:254–261. 2016. View Article : Google Scholar : PubMed/NCBI
52	Frömberg A, Rabe M and Aigner A: Multiple effects of the special AT-rich binding protein 1 (SATB1) in colon carcinoma. Int J Cancer. 135:2537–2546. 2014. View Article : Google Scholar
53	Mao L, Yang C, Wang J, Li W, Wen R, Chen J and Zheng J: SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion. J Transl Med. 11:1112013. View Article : Google Scholar : PubMed/NCBI
54	Mao LJ, Zhang J, Liu N, Fan L, Yang DR, Xue BX, Shan YX and Zheng JN: Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis. Tumor Biol. 36:9073–9081. 2015. View Article : Google Scholar : PubMed/NCBI
55	Qi H, Fu X, Li Y, Pang X, Chen S, Zhu X, Li F and Tan W: SATB1 promotes epithelial-mesenchymal transition and metastasis in prostate cancer. Oncol Lett. 13:2577–2582. 2017. View Article : Google Scholar : PubMed/NCBI
56	Wan F, Cheng C, Wang Z, Xiao X, Zeng H, Xing S, Chen X, Wang J, Li S, Zhang Y, et al: SATB1 overexpression regulates the development and progression in bladder cancer through EMT. PLoS One. 10:e01175182015. View Article : Google Scholar : PubMed/NCBI
57	Baguma-Nibasheka M, Angka HE, Inanlou MR and Kablar B: Microarray analysis of Myf5-/-:MyoD-/-hypoplastic mouse lungs reveals a profile of genes involved in pneumocyte differentiation. Histol Histopathol. 22:483–495. 2007.PubMed/NCBI
58	Selinger CI, Cooper WA, Al-Sohaily S, Mladenova DN, Pangon L, Kennedy CW, McCaughan BC, Stirzaker C and Kohonen-Corish MR: Loss of special AT-rich binding protein 1 expression is a marker of poor survival in lung cancer. J Thorac Oncol. 6:1179–1189. 2011. View Article : Google Scholar : PubMed/NCBI
59	Glatzel-Plucinska N, Piotrowska A, Grzegrzolka J, Olbromski M, Rzechonek A, Dziegiel P and Podhorska-Okolow M: SATB1 level correlates with Ki-67 expression and is a positive prognostic factor in non-small cell lung carcinoma. Anticancer Res. 38:723–736. 2018.PubMed/NCBI
60	Huang B, Zhou H, Wang S, Lang XP and Wang X: Effect of silencing SATB1 on proliferation, invasion and apoptosis of A549 human lung adenocarcinoma cells. Oncol Lett. 12:3818–3824. 2016. View Article : Google Scholar : PubMed/NCBI
61	Huang B, Zhou H, Wang X and Liu Z: Silencing SATB1 with siRNA inhibits the proliferation and invasion of small cell lung cancer cells. Cancer Cell Int. 13:82013. View Article : Google Scholar : PubMed/NCBI
62	Detterbeck FC, Boffa DJ and Tanoue LT: The new lung cancer staging system. Chest. 136:260–271. 2009. View Article : Google Scholar : PubMed/NCBI
63	Tuffaha MSA: Phenotypic and Genotypic Diagnosis of Malignancies: An Immunohistochemical and Molecular Approach. 1st edition. Wiley-VCH; 2008, View Article : Google Scholar
64	Mogilner A and Keren K: The shape of motile cells. Curr Biol. 19:R762–R771. 2009. View Article : Google Scholar : PubMed/NCBI
65	Glatzel-Plucinska N, Piotrowska A, Dziegiel P and Podhorska-Okołów M: The role of SATB1 in tumour progression and metastasis. Int J Mol Sci. 20:41562019. View Article : Google Scholar : PubMed/NCBI
66	Zhang J, Zhang B, Zhang X, Sun Y, Wei X, McNutt MA, Lu S, Liu Y, Zhang D, Wang M, et al: SATB1 expression is associated with biologic behavior in colorectal carcinoma in vitro and in vivo. PLoS One. 8:e479022013. View Article : Google Scholar : PubMed/NCBI
67	Mansour MA, Hyodo T, Akter KA, Kokuryo T, Uehara K, Nagino M and Senga T: SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer. Oncotarget. 7:4993–5006. 2016. View Article : Google Scholar : PubMed/NCBI
68	Zhang Y, Tian X, Ji H, Guan X, Xu W, Dong B, Zhao M, Wei M, Ye C, Sun Y, et al: Expression of SATB1 promotes the growth and metastasis of colorectal cancer. PLoS One. 9:e1004132014. View Article : Google Scholar : PubMed/NCBI
69	Loh CY, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, Chong PP and Looi CY: The E-Cadherin and N-Cadherin switch in epithelial-to-mesenchymal transition: Signaling, therapeutic implications, and challenges. Cells. 8:11182019. View Article : Google Scholar : PubMed/NCBI
70	Berx G and van Roy F: Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol. 1:a0031292009. View Article : Google Scholar : PubMed/NCBI
71	Bae GY, Choi SJ, Lee JS, Jo J, Lee J, Kim J and Cha HJ: Loss of E-cadherin activates EGFR-MEK/ERK signaling, which promotes invasion via the ZEB1/MMP2 axis in non-small cell lung cancer. Oncotarget. 4:2512–2522. 2013. View Article : Google Scholar : PubMed/NCBI
72	Onder TT, Gupta PB, Mani SA, Yang J, Lander ES and Weinberg RA: Loss of E-Cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 68:3645–3654. 2008. View Article : Google Scholar : PubMed/NCBI
73	Kase S, Sugio K, Yamazaki K, Okamoto T, Yano T and Sugimachi K: Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res. 6:4789–4796. 2000.PubMed/NCBI
74	Bremnes RM, Veve R, Gabrielson E, Hirsch FR, Baron A, Bemis L, Gemmill RM, Drabkin HA and Franklin WA: High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol. 20:2417–2428. 2002. View Article : Google Scholar : PubMed/NCBI
75	Yan B, Zhang W, Jiang LY, Qin WX and Wang X: Reduced E-Cadherin expression is a prognostic biomarker of non-small cell lung cancer: A meta-analysis based on 2395 subjects. Int J Clin Exp Med. 7:4352–4356. 2014.PubMed/NCBI
76	Lee YC, Wu CT, Chen CS and Chang YL: E-Cadherin expression in surgically-resected non-small cell lung cancers-A clinicopathological study. Thorac Cardiovasc Surg. 48:294–299. 2000. View Article : Google Scholar : PubMed/NCBI
77	Grigoras ML, Arghirescu TS, Folescu R, Talpoş IC, Gîndac CM, Zamfir CL, Cornianu M, Anghel MD and Levai CM: Expression of E-cadherin in lung carcinoma, other than those with small cells (NSCLC). Rom J Morphol Embryol. 58:1317–1325. 2017.PubMed/NCBI
78	Myong NH: Reduced expression of E-cadherin in human non-small cell lung carcinoma. Cancer Res Treat. 36:56–61. 2004. View Article : Google Scholar : PubMed/NCBI
79	Wu Y, Liu HB, Ding M, Liu JN, Zhan P, Fu XS and Lu G: The impact of E-cadherin expression on non-small cell lung cancer survival: A meta-analysis. Mol Biol Rep. 39:9621–9628. 2012. View Article : Google Scholar : PubMed/NCBI
80	Yang YL, Chen MW and Xian L: Prognostic and clinicopathological significance of downregulated E-cadherin expression in patients with non-small cell lung cancer (NSCLC): A meta-analysis. PLoS One. 9:e997632014. View Article : Google Scholar : PubMed/NCBI
81	Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW and Vandyke K: N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 18:9392018. View Article : Google Scholar : PubMed/NCBI
82	Luo Y, Yu T, Zhang Q, Fu Q, Hu Y, Xiang M, Peng H, Zheng T, Lu L and Shi H: Upregulated N-cadherin expression is associated with poor prognosis in epithelial-derived solid tumours: A meta-analysis. Eur J Clin Invest. 48:e129032018. View Article : Google Scholar : PubMed/NCBI
83	Hui L, Zhang S, Dong X, Tian D, Cui Z and Qiu X: Prognostic significance of twist and N-cadherin expression in NSCLC. PLoS One. 8:e621712013. View Article : Google Scholar : PubMed/NCBI
84	Sun H, Liu M, Wu X, Yang C, Zhang Y, Xu Z, Gao K and Wang F: Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma. Oncol Lett. 13:1725–1730. 2017. View Article : Google Scholar : PubMed/NCBI
85	Ozaki-Honda Y, Seki S, Fujiwara M, Matsuura M, Fujita S, Ikeda H, Umeda M, Ayuse T and Ikeda T: Prognostic prediction of oral squamous cell carcinoma by E-Cadherin and N-Cadherin expression in overall cells in tumor nests or tumor cells at the invasive front. Cancer Microenviron. 10:87–94. 2017. View Article : Google Scholar : PubMed/NCBI
86	Merikallio H, Turpeenniemi-Hujanen T, Pääkkö P, Mäkitaro R, Riitta K, Salo S, Salo T, Harju T and Soini Y: Snail promotes an invasive phenotype in lung carcinoma. Respir Res. 13:1042012. View Article : Google Scholar : PubMed/NCBI
87	Alves CC, Carneiro F, Hoefler H and Becker KF: Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. Front Biosci (Landmark Ed). 14:3035–3050. 2009. View Article : Google Scholar : PubMed/NCBI
88	Zhao Z, Rahman MA, Chen ZG and Shin DM: Multiple biological functions of Twist1 in various cancers. Oncotarget. 8:20380–20393. 2017. View Article : Google Scholar : PubMed/NCBI
89	Zhang P, Hu P, Shen H, Yu J, Liu Q and Du J: Prognostic role of Twist or Snail in various carcinomas: A systematic review and meta-analysis. Eur J Clin Invest. 44:1072–1094. 2014. View Article : Google Scholar : PubMed/NCBI
90	Huang C, Zhang P, Zhang D and Weng X: The prognostic implication of slug in all tumour patients-a systematic meta-analysis. Eur J Clin Invest. 46:398–407. 2016. View Article : Google Scholar : PubMed/NCBI
91	Yanagawa J, Walser TC, Zhu LX, Hong L, Fishbein MC, Mah V, Chia D, Goodglick L, Elashoff DA, Luo J, et al: Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin Cancer Res. 15:6820–6829. 2009. View Article : Google Scholar : PubMed/NCBI
92	Liu CW, Li CH, Peng YJ, Cheng YW, Chen HW, Liao PL, Kang JJ and Yeng MH: Snail regulates Nanog status during the epithelial-mesenchymal transition via the Smad1/Akt/GSK3β signaling pathway in non-small-cell lung cancer. Oncotarget. 5:3880–3894. 2014. View Article : Google Scholar : PubMed/NCBI
93	Jiang W, Pang XG, Wang Q, Shen YX, Chen XK and Xi JJ: Prognostic role of Twist, Slug, and Foxc2 expression in stage i non-small-cell lung cancer after curative resection. Clin Lung Cancer. 13:280–287. 2012. View Article : Google Scholar : PubMed/NCBI
94	Abd El-Rehim DM, Abd-Elghany MI and Nazmy MH: Integrin-Linked kinase, Snail and multidrug resistance protein 1: Three concordant players in the progression of non-small cell lung cancer. J Egypt Natl Canc Inst. 27:129–137. 2015. View Article : Google Scholar : PubMed/NCBI
95	Muqbil I, Wu J, Aboukameel A, Mohammad RM and Azmi AS: Snail nuclear transport: The gateways regulating epithelial-to-mesenchymal transition? Semin Cancer Biol. 27:39–45. 2014. View Article : Google Scholar : PubMed/NCBI
96	Shih JY and Yang PC: The EMT regulator slug and lung carcinogenesis. Carcinogenesis. 32:1299–1304. 2011. View Article : Google Scholar : PubMed/NCBI
97	Merikallio H, Turpeenniemi-Hujanen TT, Pääkkö P, Mäkitaro R, Kaarteenaho R, Lehtonen S, Salo S, Salo T, Harju T and Soini Y: Slug is associated with poor survival in squamous cell carcinoma of the lung. Int J Clin Exp Pathol. 7:5846–5854. 2014.PubMed/NCBI
98	Hung PF, Hong TM, Chang CC, Hung CL, Hsu YL, Chang YL, Wu CT, Chang GC, Chan NL, Yu SL, et al: Hypoxia-induced Slug SUMOylation enhances lung cancer metastasis. J Exp Clin Cancer Res. 38:52019. View Article : Google Scholar : PubMed/NCBI
99	Li M, Zhang X, Xu X, Wu J, Hu K, Guo X and Zhang P: Clinicopathological and prognostic significance of Twist overexpression in NSCLC. Oncotarget. 9:14642–14651. 2018. View Article : Google Scholar : PubMed/NCBI
100	Zeng J, Zhan P, Wu G, Yang W, Liang W, Lv T and Song Y: Prognostic value of twist in lung cancer: Systematic review and meta-analysis. Transl Lung Cancer Res. 4:236–241. 2015.PubMed/NCBI
101	Shi Y, Wu H, Zhang M, Ding L, Meng F and Fan X: Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol. 8:892013. View Article : Google Scholar : PubMed/NCBI
102	Pallier K, Cessot A, Côté JF, Just PA, Cazes A, Fabre E, Danel C, Riquet M, Devouassoux-Shisheboran M, Ansieau S, et al: TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma. PLoS One. 7:e299542012. View Article : Google Scholar : PubMed/NCBI
103	Barutçu O, Kara M, Muratlı A, Güçlü O and Dereköy S: Clinical significance of Ki-67, c-erbB-2 and E-cadherin expressions in open partial laryngectomy patients. Kulak Burun Bogaz Ihtis Derg. 26:283–292. 2016. View Article : Google Scholar
104	González-Rodilla I, Aller L, Llorca J, Muñoz AB, Verna V, Estévez J and Schneider J: The E-Cadherin expression vs. tumor cell proliferation paradox in endometrial cancer. Anticancer Res. 33:5091–5095. 2013.