Low Expression of GATA3 Promotes Cell Proliferation and Metastasis in Gastric Cancer

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2017 Dec 22

PMID 29263701

Citations 7

Authors

Shuangqin Wei

Liang Zhong

Xiaoping Wang

Wenju Zhang

Affiliations

Soon will be listed here.

Abstract

GATA3, a member of the GATA zinc finger transcription factor family, has been widely investigated for its role in cancer. Although a recent report has found that GATA3 is downregulated in gastric cancer (GC), the detailed mechanism of GATA3 in GC is still unknown. Here, we investigated whether GATA3 was downregulated in GC patients' tissue samples and cell lines using quantitative real time polymerase chain reaction and Western blotting. In addition, we conducted several functional experiments to investigate the effect of GATA3 in GC, including cell proliferation, metastasis and epithelial-mesenchymal transition (EMT). The results showed that GATA3 was downregulated in GC tissue samples and cells. Moreover, the expression of GATA3 was associated with tumor size, stage and metastasis. Restoration of GATA3 levels suppressed GC cell proliferation, migration and invasion. Furthermore, chromatin immunoprecipitation and luciferase reporter assay also revealed that GATA3 transcriptionally regulated ZEB1, thereby suppressing EMT. All these findings suggest that GATA3 serves as an oncogene in GC development.

Citing Articles

The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer.

Yan Z, Liu Y, Yuan Y Cell Death Discov. 2024; 10(1):512.

PMID: 39719478 PMC: 11668900. DOI: 10.1038/s41420-024-02275-x.

miRNAs Involvement in Modulating Signalling Pathways Involved in Ros-Mediated Oxidative Stress in Melanoma.

Escobar Moreno J, Fajardo Castiblanco J, Riano Rodriguez L, Barrios Ospina P, Zabala Bello C, Munoz Roa E Antioxidants (Basel). 2024; 13(11).

PMID: 39594467 PMC: 11591318. DOI: 10.3390/antiox13111326.

A transcription factor that promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of ovarian cancer cells and its possible mechanisms.

Qi Y, Mo K, Zhang T Biomed Eng Online. 2021; 20(1):83.

PMID: 34399777 PMC: 8366031. DOI: 10.1186/s12938-021-00919-y.

GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression.

Zhang Z, Fang X, Xie G, Zhu J Oncol Lett. 2021; 21(3):231.

PMID: 33613720 PMC: 7856699. DOI: 10.3892/ol.2021.12492.

FMNL1 Exhibits Pro-Metastatic Activity CXCR2 in Clear Cell Renal Cell Carcinoma.

Zhang M, Li Q, Yang Y, Cao Y, Zhang C Front Oncol. 2020; 10:564614.

PMID: 33324547 PMC: 7726248. DOI: 10.3389/fonc.2020.564614.

References

Martinelli P, Pau E, Cox T, Sainz Jr B, Dusetti N, Greenhalf W . GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer. Gut. 2016; 66(9):1665-1676. PMC: 5070637. DOI: 10.1136/gutjnl-2015-311256. View

de Guzman Strong C, Wertz P, Wang C, Yang F, Meltzer P, Andl T . Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3. J Cell Biol. 2006; 175(4):661-70. PMC: 2064601. DOI: 10.1083/jcb.200605057. View

Takaku M, Grimm S, Wade P . GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?. Gene Expr. 2015; 16(4):163-8. PMC: 4758516. DOI: 10.3727/105221615X14399878166113. View

Zheng R, Blobel G . GATA Transcription Factors and Cancer. Genes Cancer. 2011; 1(12):1178-88. PMC: 3092280. DOI: 10.1177/1947601911404223. View

Takai M, Terai Y, Kawaguchi H, Ashihara K, Fujiwara S, Tanaka T . The EMT (epithelial-mesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer. J Ovarian Res. 2014; 7:76. PMC: 4127950. DOI: 10.1186/1757-2215-7-76. View

Cimino-Mathews A, Subhawong A, Illei P, Sharma R, Halushka M, Vang R . GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol. 2013; 44(7):1341-9. PMC: 3991123. DOI: 10.1016/j.humpath.2012.11.003. View

Kaufman C, Zhou P, Pasolli H, Rendl M, Bolotin D, Lim K . GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 2003; 17(17):2108-22. PMC: 196453. DOI: 10.1101/gad.1115203. View

Ting C, Olson M, Barton K, Leiden J . Transcription factor GATA-3 is required for development of the T-cell lineage. Nature. 1996; 384(6608):474-8. DOI: 10.1038/384474a0. View

Ciocca V, Daskalakis C, Ciocca R, Ruiz-Orrico A, Palazzo J . The significance of GATA3 expression in breast cancer: a 10-year follow-up study. Hum Pathol. 2008; 40(4):489-95. DOI: 10.1016/j.humpath.2008.09.010. View

10.

Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra J, Houvenaeghel G . Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer. Breast Cancer Res. 2009; 11(2):R23. PMC: 2688952. DOI: 10.1186/bcr2249. View

11.

Tong Q, Dalgin G, Xu H, Ting C, Leiden J, Hotamisligil G . Function of GATA transcription factors in preadipocyte-adipocyte transition. Science. 2000; 290(5489):134-8. DOI: 10.1126/science.290.5489.134. View

12.

Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A . Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis. 2013; 34(11):2548-57. DOI: 10.1093/carcin/bgt282. View

13.

Campbell K, Whissell G, Franch-Marro X, Batlle E, Casanova J . Specific GATA factors act as conserved inducers of an endodermal-EMT. Dev Cell. 2011; 21(6):1051-61. DOI: 10.1016/j.devcel.2011.10.005. View

14.

Hong H, Zhou T, Fang S, Jia M, Xu Z, Dai Z . Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin. Breast Cancer Res Treat. 2014; 148(1):61-72. DOI: 10.1007/s10549-014-3154-9. View

15.

Deng Y, Luan F, Zeng L, Zhang Y, Ma K . MiR-429 suppresses the progression and metastasis of osteosarcoma by targeting ZEB1. EXCLI J. 2017; 16:618-627. PMC: 5491908. DOI: 10.17179/excli2017-258. View

16.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

17.

Chen C, Lin J, Chen J, Lee P, Yang C, Kuo M . Gene expression profile predicts patient survival of gastric cancer after surgical resection. J Clin Oncol. 2005; 23(29):7286-95. DOI: 10.1200/JCO.2004.00.2253. View

18.

Fan F, Samuel S, Evans K, Lu J, Xia L, Zhou Y . Overexpression of snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med. 2013; 1(1):5-16. PMC: 3544430. DOI: 10.1002/cam4.4. View

19.

Keshari R, Wang W, Zhang Y, Wang D, Li Y, Yuan S . Decreased expression of the GATA3 gene is associated with poor prognosis in primary gastric adenocarcinoma. PLoS One. 2014; 9(2):e87195. PMC: 3913598. DOI: 10.1371/journal.pone.0087195. View

20.

Grote D, Souabni A, Busslinger M, Bouchard M . Pax 2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development. 2005; 133(1):53-61. DOI: 10.1242/dev.02184. View