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Protein kinase C as a tumor suppressor
1Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0721, USA.
Seminars in Cancer Biology
|May 7, 2017
Summary
Protein kinase C (PKC) was thought to promote cancer, but new research shows it acts as a tumor suppressor. Cancer mutations often disable PKC, while enhanced activity links to diseases like Alzheimer's.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Protein kinase C (PKC) has been historically viewed as an oncoprotein due to its activation by phorbol esters.
- Decades of clinical trials targeting PKC in cancer have yielded unsuccessful results, sometimes worsening patient outcomes.
Purpose of the Study:
- To re-evaluate the role of PKC in cancer by investigating cancer-associated mutations.
- To explore the contrasting roles of PKC activity in cancer versus degenerative diseases.
Main Methods:
- Review of existing literature on PKC function, cancer mutations, and clinical trial data.
- Analysis of recent findings on PKC isozyme activity and disease association.
Main Results:
- Cancer-associated mutations in PKC are predominantly loss-of-function (LOF), suggesting a tumor-suppressive role.
- Germline mutations that increase PKC activity are linked to neurodegenerative conditions like Alzheimer's disease.
Conclusions:
- PKC family members generally function as suppressors of survival signaling, challenging the oncoprotein hypothesis.
- Understanding the precise regulation of PKC activity is crucial for therapeutic development in cancer and other diseases.
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