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The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications
Davood Zaeifi1, Khadijeh Jamialahmadi1,2, Gholamreza Karimi3,4
1Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
p66Shc is a redox-sensitive and pro-apoptotic adaptor protein that regulates oxidative stress and mitochondrial apoptosis. It is the largest of three isoforms encoded by the proto-oncogene ShcA (Src collagen homologue A). Members of the ShcA family are capable of recruiting various signalling molecules and are involved in several cellular pathways, including proliferation, growth and survival. Increasing evidence highlights the p66Shc role in various tumourigenic processes, such as cell expansion, progression, metastasis and metabolic reprogramming. This review summarises current knowledge on the role of p66Shc in cancer, explains the molecular mechanisms underlying the effects of this protein, and considers therapeutic prospects aimed at targeting it. Emerging therapeutic strategies, including small-molecule inhibitors and gene-editing approaches, are discussed alongside challenges in clinical translation.
Insights
p66Shc protein regulates oxidative stress and apoptosis, impacting cancer growth and metastasis. Targeting p66Shc offers potential therapeutic strategies for cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- p66Shc is a key adaptor protein regulating oxidative stress and apoptosis.
- It is the largest isoform of the ShcA (Src collagen homologue A) proto-oncogene.
- ShcA family members are involved in crucial cellular pathways like proliferation, growth, and survival.
Purpose of the Study:
- To review the role of p66Shc in cancer.
- To elucidate the molecular mechanisms by which p66Shc influences tumorigenesis.
- To explore therapeutic strategies targeting p66Shc.
Main Methods:
- Literature review of current knowledge on p66Shc in cancer.
- Analysis of molecular mechanisms underlying p66Shc's function.
- Discussion of emerging therapeutic approaches and clinical translation challenges.
Main Results:
- p66Shc plays a significant role in tumor progression, including cell expansion, metastasis, and metabolic reprogramming.
- Its redox-sensitive nature links oxidative stress to apoptosis and cancer development.
- Evidence supports p66Shc's involvement in various oncogenic processes.
Conclusions:
- p66Shc is a critical mediator in cancer development and progression.
- Targeting p66Shc through small-molecule inhibitors or gene editing presents promising therapeutic avenues.
- Further research is needed to overcome challenges in clinical translation of these strategies.
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