Understanding cancer: Role of DNA-dependent protein kinase in transformation of normal cells to cancer cells
Work from Dr. Mayurika Lahiri’s group from IISER Pune has shown that a cellular enzyme—DNA-dependent protein kinase (DNA-PK)—is a key player in making cells tumorigenic following exposure to alkylating agents. This finding offers a new handle in cancer treatment through the possibility of targeting DNA-PK.
Alkylating agents like cisplatin damage the DNA and keep cells from dividing. This is how they suppress cancer, where cell division goes unchecked. However, alkylating agents are not specific in targeting cancer cells, so normal cells undergo DNA damage as well.
Cells have an inherent surveillance mechanism to repair such damaged DNA. Faulty or futile repair may result in accumulation of mutations or cell death. Thus, understanding this phenomenon is critical to design novel therapeutic strategies.
Using breast epithelial cells grown in three-dimensional cultures, Dr. Lahiri’s work has shown that DNA damage though an alkylating agent can transform a non-tumorigenic cell and direct it towards acquiring tumorigenic characteristics. These characteristics were reversed by inhibiting DNA-PK, suggesting a central role for the protein.
The researchers believe that DNA-PK can serve as a potential target in treating cancer as well as targeting DNA-PK alongside the generally used DNA-damaging agents can prove to be beneficial in cancer treatment and can also prove beneficial to avoid relapse.
This work authored by Libi Anandi, Vaishali Chakravarty, K.A. Ashiq, Satish Bodakuntla, and Mayurika Lahiri is published in the Journal of Cell Science (130(21):3749-3763) and has been featured on the cover of the issue.
– Reported by Shanti Kalipatnapu with inputs from Dr. Lahiri and team