FOXO3a, a transcription factor of the forkhead family, is believed to be a tumor suppressor because it was found that inactivation of FOXO3a promoted cell transformation and tumor progression. However, recent studies demonstrate that FOXO3a may protect cells under stress conditions. A research group in China lately found that FOXO3a could promote cancer cell survival in serum starvation, which may add another layer to the complexity of the role of FOXO3a in cancer.
LI Zhaodong and ZHANG Haisheng at the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, CAS, conducted the reseasrch under the guidance of Prof. FANG Jing. They found that FOXO3a is a positive regulator of nuclear factor κB (NF-κB). Their results show that overexpression of FOXO3a increased and knockdown of FOXO3a decreased NF-κB activities. Mechanistic studies indicate that FOXO3a activate NF-κB through inducing expression of B-cell lymphoma/leukemia 10 (BCL10), an upstream regulator of NF-κB signaling. Serum deprivation activated NF-κB, which was blocked by inhibition of FOXO3a.
Their further studies showed that knockdown of FOXO3a enhanced apoptosis of cancer cells under serum-free conditions, which was prevented by overexpression of BCL10. These results suggest that FOXO3a protects cancer cells under serum deprivation condition, probably through BCL10/NF-κB. These findings combined with previous reported function of FOXO3a as a tumor suppressor also suggest that FOXO3a plays double-edged roles in tumorigenesis are double-edged. Therefore, caution should be taken when FOXO3a is employed as a target for cancer therapy.
These results have been published in Journal of Biological Chemistry on May 18, 2012. This project was supported by National Natural Science Foundation of China, Ministry of Science and Technology of China, and Chinese Academy of Sciences.
AUTHOR CONTACT:
FANG Jing, Principal Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai, China
Tel: 86-21-54920241
Email: jfang@sibs.ac.cn
Location: 
