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Published on: August 25, 2021
Tumor Suppressors Having Oncogenic Functions: The Double Agents
Neerajana Datta1, Shrabastee Chakraborty1, Malini Basu2
1Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
Abstract:
Cancer progression involves multiple genetic and epigenetic events, which involve gain-of-functions of oncogenes and loss-of-functions of tumor suppressor genes. Classical tumor suppressor genes are recessive in nature, anti-proliferative, and frequently found inactivated or mutated in cancers. However, extensive research over the last few years have elucidated that certain tumor suppressor genes do not conform to these standard definitions and might act as "double agents", playing contrasting roles in vivo in cells, where either due to haploinsufficiency, epigenetic hypermethylation, or due to involvement with multiple genetic and oncogenic events, they play an enhanced proliferative role and facilitate the pathogenesis of cancer. This review discusses and highlights some of these exceptions; the genetic events, cellular contexts, and mechanisms by which four important tumor suppressors-pRb, PTEN, FOXO, and PML display their oncogenic potentials and pro-survival traits in cancer.
Insights
Some tumor suppressor genes act as double agents in cancer, promoting proliferation through mechanisms like haploinsufficiency or epigenetic changes. This review examines how pRb, PTEN, FOXO, and PML exhibit oncogenic potential in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Cancer progression involves oncogene activation and tumor suppressor gene inactivation.
- Traditionally, tumor suppressor genes are recessive and anti-proliferative.
- Recent findings reveal some tumor suppressors act as 'double agents' with dual roles.
Purpose of the Study:
- To review exceptions to the classical tumor suppressor gene definition.
- To highlight how specific tumor suppressors can promote cancer.
- To explore the mechanisms behind these dual roles in cancer pathogenesis.
Main Methods:
- Literature review of genetic and epigenetic events in cancer.
- Analysis of cellular contexts and mechanisms of tumor suppressor gene function.
- Focus on four key tumor suppressors: pRb, PTEN, FOXO, and PML.
Main Results:
- Certain tumor suppressor genes can exhibit oncogenic potential.
- Mechanisms include haploinsufficiency, epigenetic hypermethylation, and interaction with oncogenic events.
- pRb, PTEN, FOXO, and PML can display pro-proliferative and pro-survival traits in cancer.
Conclusions:
- The role of tumor suppressor genes in cancer is more complex than previously thought.
- Understanding these 'double agent' functions is crucial for cancer therapy.
- Further research into these exceptions can reveal new therapeutic targets.
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