The role of E2F2 in signaling pathways associated with cancer pathogenesis and potential treatment: A review of current studies Review article

Main Article Content

Julia Domańska
Kamil Poboży
Paweł Domański
Marta Fudalej
Andrzej Deptała
Anna Badowska-Kozakiewicz


Introduction and objective. E2F transcription factor 2 (E2F2) protein is the transcription factor that plays an important role in tumorigenesis. E2F2 effects the cell cycle, tumor suppressor proteins, and can also be transformed by proteins of small DNA tumor viruses. The objective of the study is to provide a summary of the current knowledge on the neoplastic pathways that involve E2F2.

State of knowledge. Numerous studies have demonstrated a role for E2F2 in various signaling pathways. Certain components of these pathways may serve as potential targets for oncological therapy. E2F2 has been shown to be associated with neoplasms of various locations and histological types (breast, colon, gastric, laryngeal, liver, lung, ovarian, pancreatic, and prostate cancers).

Conclusions. Further investigations of E2F2 pathways are warranted for a clearer understanding of neoplastic processes and to identify novel pharmacological treatments. 


Download data is not yet available.


Metrics Loading ...

Article Details

How to Cite
Domańska J, Poboży K, Domański P, Fudalej M, Deptała A, Badowska-Kozakiewicz A. The role of E2F2 in signaling pathways associated with cancer pathogenesis and potential treatment: A review of current studies. OncoReview [Internet]. 2023Jul.18 [cited 2024Jul.18];13(2(50):58-6. Available from:


1. Latchman DS. Transcription factors: an overview. Int J Biochem Cell Biol. 1997; 29(12): 1305-12. .
2. Zhou Q, Zhang F, He Z et al. E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer. Front Oncol. 2019; 9: 161.
3. Broeker CD, Andrechek ER. E2F Transcription Factors in Cancer, More than the Cell Cycle. Comprehensive Pharmacology 2022.
4. Du K, Sun S, Jiang T et al. E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. Int J Biol Sci. 2022; 18(10): 4151-70.
5. Sherr CJ, McCormick F. The RB and p53 pathways in cancer. Cancer Cell. 2002; 2(2): 103-12.
6. Azechi H, Nishida N, Fukuda Y et al. Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology. 2001; 60(4): 346-54.
7. Di Fiore R, D’Anneo A, Tesoriere G et al. RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. J Cell Physiol. 2013; 228(8): 1676-87.
8. Kent LN, Leone G. The broken cycle: E2F dysfunction in cancer. Nat Rev Cancer. 2019; 19(6): 326-38.
9. Viatour P, Sage J. Newly identified aspects of tumor suppression by RB. Dis Model Mech. 2011; 4(5): 581-5.
10. Aksoy O, Chicas A, Zeng T et al. The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence. Genes Dev. 2012; 26(14): 1546-57.
11. Shamir ER, Devine WP, Pekmezci M et al. Identification of high-risk human papillomavirus and Rb/E2F pathway genomic alterations in mutually exclusive subsets of colorectal neuroendocrine carcinoma. Mod Pathol. 2019; 32(2): 290-305.
12. Database, GeneCards Human Gene. “E2F2 Gene (Protein Coding).” GeneCards (access: 19.07.2023).
13. Wu L, Timmers C, Maiti B et al. The E2F1-3 transcription factors are essential for cellular proliferation. Nature. 2001; 414(6862): 457-62.
14. Timmers C, Sharma N, Opavsky R et al. E2f1, E2f2, and E2f3 control E2F target expression and cellular proliferation via a p53-dependent negative feedback loop. Mol Cell Biol. 2007; 27(1): 65-78. (correction in: Mol Cell Biol. 2012; 32(9): 1758).
15. Sharma N, Timmers C, Trikha P et al. Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S progression and cellular transformation. J Biol Chem. 2006; 281(47): 36124-31.
16. Chafin CB, Regna NL, Caudell DL et al. MicroRNA-let-7a promotes E2F-mediated cell proliferation and NFκB activation in vitro. Cell Mol Immunol. 2014; 11(1): 79-83.
17. Wang S, Wang L, Wu C et al. E2F2 directly regulates the STAT1 and PI3K/AKT/NF-κB pathways to exacerbate the inflammatory phenotype in rheumatoid arthritis synovial fibroblasts and mouse embryonic fibroblasts. Arthritis Res Ther. 2018; 20(1): 225.
18. Zhang R, Wang L, Pan JH et al. A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis. Sci Rep. 2018; 8(1): 2623.
19. Yoon SO, Shin S, Mercurio AM. Ras stimulation of E2F activity and a consequent E2F regulation of integrin alpha6beta4 promote the invasion of breast carcinoma cells. Cancer Res. 2006; 66(12): 6288-95.
20. Stravopodis DJ, Karkoulis PK, Konstantakou EG et al. Thymidylate synthase inhibition induces p53-dependent and p53-independent apoptotic responses in human urinary bladder cancer cells. J Cancer Res Clin Oncol. 2011; 137(2): 359-74.
21. Li L, Wang S, Zhang Y et al. The E2F transcription factor 2: What do we know? Biosci Trends. 2021; 15(2): 83-92.
22. Azkargorta M, Fullaondo A, Laresgoiti U et al. Differential proteomics analysis reveals a role for E2F2 in the regulation of the Ahr pathway in T lymphocytes. Mol Cell Proteomics. 2010; 9(10): 2184-94.
23. Ebelt H, Hufnagel N, Neuhaus P et al. Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis. Circ Res. 2005; 96(5): 509-17.
24. Iglesias A, Murga M, Laresgoiti U et al. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice. J Clin Invest. 2004; 113(10): 1398-407.
25. Raj D, Liu T, Samadashwily G et al. Survivin repression by p53, Rb and E2F2 in normal human melanocytes. Carcinogenesis. 2008; 29(1): 194-201.
26. Chen D, Chen Y, Forrest D et al. E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3. Cell Death Differ. 2013; 20(7): 931-40.
27. Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity. Immunity. 2001; 15(6): 959-70.
28. Wu J, Sabirzhanov B, Stoica BA et al. Ablation of the transcription factors E2F1-2 limits neuroinflammation and associated neurological deficits after contusive spinal cord injury. Cell Cycle. 2015; 14(23): 3698-3712.
29. Lammens T, Li J, Leone G et al. Atypical E2Fs: new players in the E2F transcription factor family. Trends Cell Biol. 2009; 19(3): 111-8.
30. Karlseder J, Rotheneder H, Wintersberger E. Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. Mol Cell Biol. 1996; 16(4): 1659-67.
31. Mattiuzzi C, Lippi G. Current Cancer Epidemiology. J Epidemiol Glob Health. 2019; 9(4): 217-22.
32. Elledge SJ. Cell cycle checkpoints: preventing an identity crisis. Science. 1996; 274(5293): 1664-72.
33. Ozaki T, Nakagawara A. Role of p53 in Cell Death and Human Cancers. Cancers (Basel). 2011; 3(1): 994-1013.
34. Cancer Today. Estimated age-standardized incidence rates (World) in 2020, World, both sexes, all ages (excl. NMSC) (access: 19.04.2023).
35. Bollig-Fischer A, Marchetti L, Mitrea C et al. Modeling time-dependent transcription effects of HER2 oncogene and discovery of a role for E2F2 in breast cancer cell-matrix adhesion. Bioinformatics. 2014; 30(21): 3036-43.
36. Lin QY, Wang JQ, Wu LL et al. miR-638 represses the stem cell characteristics of breast cancer cells by targeting E2F2. Breast Cancer. 2020; 27(1): 147-58.
37. Buccafusca G, Proserpio I, Tralongo AC et al. Early colorectal cancer: diagnosis, treatment and survivorship care. Crit Rev Oncol Hematol. 2019; 136: 20-30.
38. Li T, Luo W, Liu K et al. miR-31 promotes proliferation of colon cancer cells by targeting E2F2. Biotechnol Lett. 2015; 37(3): 523-32.
39. Wen L, Cheng F, Zhou Y et al. MiR-26a enhances the sensitivity of gastric cancer cells to cisplatin by targeting NRAS and E2F2. Saudi J Gastroenterol. 2015; 21(5): 313-9.
40. Wang H, Zhang X, Liu Y et al. Downregulated miR-31 level associates with poor prognosis of gastric cancer and its restoration suppresses tumor cell malignant phenotypes by inhibiting E2F2. Oncotarget. 2016; 7(24): 36577-89.
41. Yu J, Fang C, Zhang Z et al. H19 Rises in Gastric Cancer and Exerts a Tumor-Promoting Function via miR-138/E2F2 Axis. Cancer Manag Res. 2020; 12: 13033-42.
42. Cui X, Xiao D, Cui Y et al. Exosomes-Derived Long Non-Coding RNA HOTAIR Reduces Laryngeal Cancer Radiosensitivity by Regulating microRNA-454-3p/E2F2 Axis. Onco Targets Ther. 2019; 12: 10827-39.
43. Hong SH, Eun JW, Choi SK et al. Epigenetic reader BRD4 inhibition as a therapeutic strategy to suppress E2F2-cell cycle regulation circuit in liver cancer. Oncotarget. 2016; 7(22): 32628-40.
44. Zeng Z, Cao Z, Tang Y. Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data. BMC Cancer. 2020; 20(1): 1037.
45. Zeng Z, Jiang W, Kan J et al. Shentao Ruangan formula promotes apoptosis via the E2F2-p53 pathway in hepatocellular carcinoma. Phytomedicine. 2023; 109: 154565.
46. Shen S, Wang Y. Expression and Prognostic Role of E2F2 in Hepatocellular Carcinoma. Int J Gen Med. 2021; 14: 8463-72.
47. Feliciano A, Garcia-Mayea Y, Jubierre L et al. miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer. Cell Death Dis. 2017; 8(10): e3141.
48. Zhou X, Tao H. Overexpression of microRNA-936 suppresses non-small cell lung cancer cell proliferation and invasion via targeting E2F2. Exp Ther Med. 2018; 16(3): 2696-702.
49. Li X, Zhang Z, Jiang H et al. Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer. Cell Physiol Biochem. 2018; 51(5): 2324-40.
50. Zhang H, Tulahong A, Wang W et al. Downregulation of microRNA-519 enhances development of lung cancer by mediating the E2F2/PI3K/AKT axis. Int J Clin Exp Pathol. 2020; 13(4): 711-20.
51. Jiang N, Dai Q, Su X et al. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Mol Biol Rep. 2020; 47(6): 4587-629.
52. Huang JW, Luo XY, Li ZH et al. LncRNA NNT-AS1 regulates the progression of lung cancer through the NNT-AS1/miR-3666/E2F2 axis. Eur Rev Med Pharmacol Sci. 2020; 24(1): 238-48.
53. Xie L, Li T, Yang LH. E2F2 induces MCM4, CCNE2 and WHSC1 upregulation in ovarian cancer and predicts poor overall survival. Eur Rev Med Pharmacol Sci. 2017; 21(9): 2150-6.
54. Cao J, Wang H, Liu G et al. LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging. J Cell Mol Med. 2021; 25(2): 1178-89.
55. Yao Z, Chen Q, Ni Z et al. Long Non-Coding RNA Differentiation Antagonizing Nonprotein Coding RNA (DANCR) Promotes Proliferation and Invasion of Pancreatic Cancer by Sponging miR-214-5p to Regulate E2F2 Expression. Med Sci Monit. 2019; 25: 4544-52.
56. Dong Q, Meng P, Wang T et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010; 5(4): e10147.