Prognostic value of MTA1, SOX4 and EZH2 expression in esophageal squamous cell carcinoma

Liu,Wenying; Xia,Yu; Li,Mengyan; Abulajiang,Gulinaer; Wang,Hui; Su,Liping; Li,Chao; Shi,Yan; Zhang,Wenjing; Xu,Shanshan; Ma,Yuqing

doi:10.3892/etm.2021.10154

Prognostic value of MTA1, SOX4 and EZH2 expression in esophageal squamous cell carcinoma

Authors:
- Wenying Liu
- Yu Xia
- Mengyan Li
- Gulinaer Abulajiang
- Hui Wang
- Liping Su
- Chao Li
- Yan Shi
- Wenjing Zhang
- Shanshan Xu
- Yuqing Ma
View Affiliations

Affiliations: Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China, Department of Respiratory Medicine, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
Published online on: May 3, 2021 https://doi.org/10.3892/etm.2021.10154
Article Number: 722
Copyright: © Liu 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

Esophageal cancer has always been one of the major malignant tumor types affecting the health of the Chinese population. Metastasis‑associated protein 1 (MTA1), SOX4 and enhancer of zeste homolog 2 (EZH2) are all potent inducers of invasion and metastasis in esophageal squamous cell carcinoma (ESCC). However, the role of these signaling molecules and their implication in ESCC have remained largely elusive. In the present study, the effects of MTA1, SOX4 and EZH2 on the prognosis of patients with ESCC were explored. Immunohistochemistry was used to examine the expression levels of MTA1, SOX4 and EZH2. The χ² test was used to analyze the association between protein expression and clinicopathological parameters. Kaplan‑Meier curves and Cox proportional hazards model survival analysis was performed to investigate the effects of the three proteins examined on disease prognosis. The results indicated that MTA1 may be used as a prognostic and diagnostic marker for ESCC. To the best of our knowledge, the present study was the first to demonstrate that MTA1‑SOX4 signaling is associated with prognosis in ESCC. However, no significant association was noted between SOX4 and EZH2 in the present study, which was inconsistent with previously reported findings. The function of the MTA1‑SOX4‑EZH2 axis and the interactions of the proteins involved require further investigation.

View Figures

View References

1	Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X, Sato Y, Okuno Y, Varela AM, Ding LW, et al: Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet. 46:467–473. 2014.PubMed/NCBI View Article : Google Scholar
2	Jain R, Gupta S, Pasricha N, Faujdar M, Sharma M and Mishra P: ESCC with metastasis in the young age of caustic ingestion of shortest duration. J Gastrointest Cancer. 41:93–95. 2010.PubMed/NCBI View Article : Google Scholar
3	Liu Q, Liang M, Liu T, Vuitton L, Zheng S, Gao X, Lu M, Li X, Sheyhidin I and Lu X: M2 isoform of pyruvate kinase (PKM2) is upregulated in Kazakh's ESCC and promotes proliferation and migration of ESCC cells. Tumour Biol. 37:2665–2672. 2016.PubMed/NCBI View Article : Google Scholar
4	Encinas de la Iglesia J, Corral de la Calle MA, Fernandez Perez GC, Ruano Perez R and Alvarez Delgado A: Esophageal cancer: Anatomic particularities, staging, and imaging techniques. Radiologia. 58:352–365. 2016.PubMed/NCBI View Article : Google Scholar
5	Liu B, Bo Y, Wang K, Liu Y, Tang X, Zhao Y, Zhao E and Yuan L: Concurrent neoadjuvant chemoradiotherapy could improve survival outcomes for patients with esophageal cancer: A meta-analysis based on random clinical trials. Oncotarget. 8:20410–20417. 2017.PubMed/NCBI View Article : Google Scholar
6	Zhou YX, Liu Q, Wang H, Ding F and Ma YQ: The expression and prognostic value of SOX2, β-catenin and survivin in esophageal squamous cell carcinoma. Future Oncol. 15:4181–4195. 2019.PubMed/NCBI View Article : Google Scholar
7	Chen Q, Zheng PS and Yang WT: EZH2-mediated repression of GSK-3β and TP53 promotes Wnt/β-catenin signaling-dependent cell expansion in cervical carcinoma. Oncotarget. 7:36115–36129. 2016.PubMed/NCBI View Article : Google Scholar
8	Moon HE, Cheon H, Chun KH, Lee SK, Kim YS, Jung BK, Park JA, Kim SH, Jeong JW and Lee MS: Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1alpha. Oncol Rep. 16:929–935. 2006.PubMed/NCBI
9	Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su IH, Hannon G, Tarakhovsky A and Fuchs E: Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell. 136:1122–1135. 2009.PubMed/NCBI View Article : Google Scholar
10	Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT and Tarakhovsky A: Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 4:124–131. 2003.PubMed/NCBI View Article : Google Scholar
11	Nienstedt JC, Schroeder C, Clauditz T, Simon R, Sauter G, Muenscher A, Blessmann M, Hanken H and Pflug C: EZH2 overexpression in head and neck cancer is related to lymph node metastasis. J Oral Pathol Med. 47:240–245. 2018.PubMed/NCBI View Article : Google Scholar
12	Feng H, Yu Z, Tian Y, Lee YY, Li MS, Go MY, Cheung YS, Lai PB, Chan AM, To KF, et al: A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogenesis and associates with tumor recurrence and poor survival of patients. J Hepatol. 62:1100–1111. 2015.PubMed/NCBI View Article : Google Scholar
13	Parvani JG and Schiemann WP: Sox4, EMT programs, and the metastatic progression of breast cancers: Mastering the masters of EMT. Breast Cancer Res. 15(R72)2013.PubMed/NCBI View Article : Google Scholar
14	Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schubeler D, van Nimwegen E and Christofori G: Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 23:768–783. 2013.PubMed/NCBI View Article : Google Scholar
15	Lin L, Wang Z, Jin H, Shi H, Lu Z and Qi Z: miR-212/132 is epigenetically downregulated by SOX4/EZH2-H3K27me3 feedback loop in ovarian cancer cells. Biol: Nov 3, 2016 (Epub ahead of print).
16	Moreno CS: SOX4: The unappreciated oncogene. Semin Cancer Biol. 67:57–64. 2020.PubMed/NCBI View Article : Google Scholar
17	David CJ, Huang YH, Chen M, Su J, Zou Y, Bardeesy N, Iacobuzio-Donahue CA and Massague J: TGF-β tumor suppression through a lethal EMT. Cell. 164:1015–1030. 2016.PubMed/NCBI View Article : Google Scholar
18	Wang L, Zhang J, Yang X, Chang YW, Qi M, Zhou Z, Zhang J and Han B: SOX4 is associated with poor prognosis in prostate cancer and promotes epithelial-mesenchymal transition in vitro. Prostate Cancer Prostatic Dis. 16:301–307. 2013.PubMed/NCBI View Article : Google Scholar
19	Jafarnejad SM, Wani AA, Martinka M and Li G: Prognostic significance of Sox4 expression in human cutaneous melanoma and its role in cell migration and invasion. Am J Pathol. 177:2741–2752. 2010.PubMed/NCBI View Article : Google Scholar
20	Zhang J, Liang Q, Lei Y, Yao M, Li L, Gao X, Feng J, Zhang Y, Gao H, Liu DX, et al: SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression. Cancer Res. 72:4597–4608. 2012.PubMed/NCBI View Article : Google Scholar
21	Koumangoye RB, Andl T, Taubenslag KJ, Zilberman ST, Taylor CJ, Loomans HA and Andl CD: SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells. Mol Cancer. 14(24)2015.PubMed/NCBI View Article : Google Scholar
22	Nan P, Wang T, Li C, Li H, Wang J, Zhang J, Dou N, Zhan Q, Wang H and Qian H: MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway. Carcinogenesis. 41:1263–1272. 2020.PubMed/NCBI View Article : Google Scholar
23	Hannafon BN, Gin AL, Xu YF, Bruns M, Calloway CL and Ding WQ: Metastasis-associated protein 1 (MTA1) is transferred by exosomes and contributes to the regulation of hypoxia and estrogen signaling in breast cancer cells. Cell Commun Signal. 17(13)2019.PubMed/NCBI View Article : Google Scholar
24	Deng L, Tang J, Yang H, Cheng C, Lu S, Jiang R and Sun B: MTA1 modulated by miR-30e contributes to epithelial-to-mesenchymal transition in hepatocellular carcinoma through an ErbB2-dependent pathway. Oncogene. 36:3976–3985. 2017.PubMed/NCBI View Article : Google Scholar
25	Liu J, Xu D, Wang H, Zhang Y, Chang Y, Zhang J, Wang J, Li C, Liu H, Zhao M, et al: The subcellular distribution and function of MTA1 in cancer differentiation. Oncotarget. 5:5153–5164. 2014.PubMed/NCBI View Article : Google Scholar
26	Xue H, Wang H, Liu J, Liu H, Li C, Han L, Lin C, Zhan Q, Zhao Z and Qian H: MTA1 downregulation inhibits malignant potential in a small cell lung cancer cell line. Oncol Rep. 33:885–892. 2015.PubMed/NCBI View Article : Google Scholar
27	Dhar S, Kumar A, Gomez CR, Akhtar I, Hancock JC, Lage JM, Pound CR and Levenson AS: MTA1-activated Epi-microRNA-22 regulates E-cadherin and prostate cancer invasiveness. FEBS Lett. 591:924–933. 2017.PubMed/NCBI View Article : Google Scholar
28	Guo N, Shen G, Zhang Y, Moustafa AA, Ge D and You Z: Interleukin-17 promotes migration and invasion of human cancer cells through upregulation of MTA1 expression. Front Oncol. 9(546)2019.PubMed/NCBI View Article : Google Scholar
29	Yoo YG, Kong G and Lee MO: Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J. 25:1231–1241. 2006.PubMed/NCBI View Article : Google Scholar
30	Weng W, Yin J, Zhang Y, Qiu J and Wang X: Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin. Int J Oncol. 44:812–818. 2014.PubMed/NCBI View Article : Google Scholar
31	Song Q, Wang B, Liu M, Ren Z, Fu Y, Zhang P and Yang M: MTA1 promotes the invasion and migration of oral squamous carcinoma by inducing epithelial-mesenchymal transition via the hedgehog signaling pathway. Exp Cell Res. 382(111450)2019.PubMed/NCBI View Article : Google Scholar
32	Edge S, Byrd DR and Compton CC: AJCC Cancer Staging Manual (7th edition). Springer International Publishing: American Joint Commission on Cancer, 2009.
33	Zhou N, Wang H, Liu H, Xue H, Lin F, Meng X, Liang A, Zhao Z, Liu Y and Qian H: MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer. J Exp Clin Cancer Res. 34(157)2015.PubMed/NCBI View Article : Google Scholar
34	Matsubara T, Toyokawa G, Takada K, Kinoshita F, Kozuma Y, Akamine T, Shimokawa M, Haro A, Osoegawa A, Tagawa T and Mori M: The association and prognostic impact of enhancer of zeste homologue 2 expression and epithelial-mesenchymal transition in resected lung adenocarcinoma. PLoS One. 14(e0215103)2019.PubMed/NCBI View Article : Google Scholar
35	Toh Y and Nicolson GL: Properties and clinical relevance of MTA1 protein in human cancer. Cancer Metastasis Rev. 33:891–900. 2014.PubMed/NCBI View Article : Google Scholar
36	Wang Q, Wang F, Lv J, Xin J, Xie L, Zhu W, Tang Y, Li Y, Zhao X, Wang Y, et al: Interactive online consensus survival tool for esophageal squamous cell carcinoma prognosis analysis. Oncol Lett. 18:1199–1206. 2019.PubMed/NCBI View Article : Google Scholar
37	Li L, Liu J, Xue H, Li C, Liu Q, Zhou Y, Wang T, Wang H, Qian H and Wen T: A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis. Oncogene. 39:2125–2139. 2020.PubMed/NCBI View Article : Google Scholar