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Deciphering ETS2: An indispensable conduit to cancer
Samu John1, Dhanya Kalathil2, Ramesh Pothuraju3
1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India; Research Centre, University of Kerala, Thiruvananthapuram 695034, India; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Abstract:
E26 Transformation-Specific homolog 2 (ETS2) is a founding member of the ETS family of transcription factors and has been implicated in several developmental and survival functions. The predominant route of its action is by directly binding and regulating the promoters of its target genes, although it can function through other regulatory mechanisms as well. In this review, a comprehensive understanding of the contribution of ETS2 in health and disease is described with specific focus on cancer. ETS2 demonstrates extreme complexity as it can act as a double-edged sword in cancer with tumour suppressive or oncogenic functions in a context specific manner. Here, we delineate the different signalling pathways, post-translational modifications, miRNA regulations and protein-protein interactions that illustrate the role of ETS2 as an emerging biomarker with special emphasis on its contribution to 'hallmarks of cancer'. Given the evidently opposing effects of ETS2 in different cancers, elucidating the critical mechanisms in its development and progression can validate ETS2's potential as a novel therapeutic target. Finally, we provide insights into frontier areas of research focus that implicate ETS2 and can translate into clinical outcomes.
Insights
E26 Transformation-Specific homolog 2 (ETS2) acts as a double-edged sword in cancer, exhibiting both tumor-suppressive and oncogenic roles. Understanding ETS2
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- E26 Transformation-Specific homolog 2 (ETS2) is a key transcription factor involved in cellular development and survival.
- ETS2 primarily functions by regulating target gene promoters but also utilizes other mechanisms.
- Its role in cancer is complex, acting as both a tumor suppressor and an oncogene depending on the context.
Purpose of the Study:
- To provide a comprehensive review of ETS2's role in health and disease, with a focus on cancer.
- To explore the signaling pathways, post-translational modifications, miRNA regulations, and protein-protein interactions involving ETS2.
- To highlight ETS2's potential as a biomarker and therapeutic target in oncology.
Main Methods:
- Literature review and synthesis of existing research on ETS2.
- Analysis of ETS2's involvement in the 'hallmarks of cancer'.
- Discussion of regulatory mechanisms including signaling pathways, PTMs, miRNA, and PPIs.
Main Results:
- ETS2 exhibits context-specific dual roles (tumor suppressive or oncogenic) in various cancers.
- ETS2 is implicated in multiple 'hallmarks of cancer', influencing tumor development and progression.
- Various regulatory mechanisms (signaling, PTMs, miRNA, PPIs) modulate ETS2 function.
Conclusions:
- ETS2 is a complex factor with significant implications in cancer, acting as a potential biomarker.
- Elucidating ETS2's precise mechanisms in different cancer contexts is crucial for therapeutic development.
- Further research into ETS2 could lead to novel clinical strategies and outcomes.
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