ELF3 as an important factor in carcinogenesis – a brief review of the recent studies Review article

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Julia Domańska
Kamil Poboży
Michał Kuryłek
Marta M. Fudalej
Aleksandra Sobiborowicz
Andrzej Deptała
Anna M. Badowska-Kozakiewicz


Introduction and objective: E74-like transcription factor 3 (ELF3) is mainly expressed in epithelial tissue, being responsible for differentiation and regeneration. Furthermore, it plays a role in inflammation, remodeling, allergy regulation and apoptosis. Various studies on ELF3 conducted since 1997 have also proved its connection with carcinogenesis and metastasis. This review summarizes recent advances in understanding the role of ELF3 in the following cancers: ampullary, bladder, breast, gastric, hepatocellular, nasopharyngeal, thyroid, lung and ovarian ones.

State of knowledge: There are still many unresolved and undiscovered issues regarding ELF3 mutations, however, based on research since 2016, a link to many signaling pathways important for carcinogenesis has been shown. There is no simple correlation between a specific ELF3 mutation and effect on cancer cells. In various types of cancers, ELF3 is associated with other pathways, and modifications exerted by silencing or amplifying its or associated genes, cause different effects in patient prediction. An example of the effect of ELF3 on tumor progression is achieved by negatively regulating the ZEB1 transcription factor responsible for metastasis. WNT, RAS, Akt, mTOR, HER2, Cyclin D, IRF6 are other ELF3-related factors that affects pathways crucial for tumorigenesis.

Conclusions: Further research and attempts to use ELF3 in the treatment and prognosis of cancer appear to be beneficial

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How to Cite
Domańska J, Poboży K, Kuryłek M, Fudalej MM, Sobiborowicz A, Deptała A, Badowska-Kozakiewicz AM. ELF3 as an important factor in carcinogenesis – a brief review of the recent studies. OncoReview [Internet]. 2020Sep.30 [cited 2020Oct.30];10(2(38):77-1. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/1071


1. Oettgen P, Carter KC, Augustus M et al. The novel epithelial-specific Ets transcription factor gene ESX maps to human chromosome 1q32.1. Genomics. 1997; 45(2): 456-7.
2. Sengez B, Aygun I, Shehwana H et al. The Transcription Factor Elf3 Is Essential for a Successful Mesenchymal to Epithelial Transition. Cells. 2019; 8(8): 858.
3. Luk IY, Reehorst CM, Mariadason JM. ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer. Molecules. 2018; 23(9): 2191.
4. Kopp JL, Wilder PJ, Desler M et al. Unique and selective effects of five Ets family members, Elf3, Ets1, Ets2, PEA3, and PU.1, on the promoter of the type II transforming growth factor-beta receptor gene. J Biol Chem. 2004; 279(19): 19407-20.
5. Liu D, Skomorovska Y, Song J et al. ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1. Cancer Biol Ther. 2019; 20(1): 90-100.
6. Alotaibi H, Basilicata MF, Shehwana H et al. Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition. Biochim Biophys Acta. 2015; 1849(6): 731-42.
7. Yachida S, Wood LD, Suzuki M et al. Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. Cancer Cell. 2016; 29(2): 229-40.
8. Gingras MC, Covington KR, Chang DK et al. Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. Cell Rep. 2016; 14(4): 907-19.
9. Gondkar K, Patel K, Krishnappa S et al. E74 like ETS transcription factor 3 (ELF3) is a negative regulator of epithelial-mesenchymal transition in bladder carcinoma. Cancer Biomark. 2019; 25(2): 223-32.
10. World Health Organization International Agency for Research on Cancer. The Global Cancer Observatory. 2018 statistics. http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
11. Gajulapalli VN, Samanthapudi VS, Pulaganti M et al. A transcriptional repressive role for epithelial-specific ETS factor ELF3 on oestrogen receptor alpha in breast cancer cells. Biochem J. 2016; 473(8): 1047-61.
12. Kar A, Gutierrez-Hartmann A. ESE-1/ELF3 mRNA expression associates with poor survival outcomes in HER2(+) breast cancer patients and is critical for tumorigenesis in HER2(+) breast cancer cells. Oncotarget. 2017; 8(41): 69622-40.
13. Li D, Cheng P, Wang J et al. IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer. Front Oncol. 2019; 9: 220.
14. Zheng L, Xu M, Xu J, et al. ELF3 promotes epithelial-mesenchymal transition by protecting ZEB1 from miR-141-3p-mediated silencing in hepatocellular carcinoma. Cell Death Dis. 2018; 9(3): 387.
15. Ke Z, Xie F, Zheng C et al. CircHIPK3 promotes proliferation and invasion in nasopharyngeal carcinoma by abrogating miR-4288-induced ELF3 inhibition. J Cell Physiol. 2019; 234(2): 1699-706.
16. Chen H, Chen W, Zhang X et al. E26 transformation (ETS) specific related transcription factor 3 (ELF3) orchestrates a positive feedback loop that constitutively activates the MAPK/Erk pathway to drive thyroid cancer. Oncol Rep. 2019; 41(1): 570-8.
17. Wang H, Yu Z, Huo S et al. Overexpression of ELF3 facilitates cell growth and metastasis through PI3K/Akt and ERK signaling pathways in non-small cell lung cancer. Int J Biochem Cell Biol. 2018; 94: 98-106.
18. Enfield KSS, Marshall EA, Anderson C et al. Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma. Nat Commun. 2019; 10(1): 5438.
19. Yeung TL, Leung CS, Wong KK et al. ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells. Oncotarget. 2017; 8(10): 16951-63.

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