Molecular biology: Eliminate to survive
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Molecular biology: Eliminate to survive
Published online: 4 August 2010 | doi:10.1038/nchina.2010.87
Felix Cheung
A protein that induces autophagy may help to suppress tumour growth
Original article citation
Zhao, Y. et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nature Cell Biol. doi:10.1038/ncb2069 (2010).
© (2010) Nature Cell Biology
Although previous studies have highlighted the possible link between autophagy — the cellular process for eliminating damaged proteins and organelles in the cytosol — and tumour suppression, the exact mechanism that connects them is still unknown.
Weiguo Zhu and co-workers at Peking University in Beijing[1] have now identified a protein that induces both autophagy and tumour suppressor activity.
Recent reports have suggested that FoxO proteins are involved in the induction of autophagy. The researchers found that in response to stress, human cancer cell lines increased their cytosolic FoxO1 expression, p62 degradation and LC3-II accumulation (the latter two being the markers of autophagy). Importantly, they found that FoxO1 underwent acetylation to trigger autophagy.
Further investigation revealed that during the process of acetylation, FoxO1 detaches from SIRT2, a histone deacetylase, and binds to Atg7, an E1-like protein involved in autophagosome formation.
Human cancer cells expressing FoxO1 stopped growing in mice (pictured right), but those expressing an empty vector continued to grow (pictured left). The researchers also compared tissue samples from normal patients and patients with colon cancer. They found that the FoxO1 expression and p62 degradation levels were much lower in cancerous tissues.
The results clearly demonstrate a connection between autophagy and tumour suppressor activity. The researchers believe that autophagy could offer a method of suppressing tumour growth, but more work is required to understand how autophagy achieves this.
The authors of this work are from:
Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University, Peking University, Beijing, China; Department of Surgery, Secondary Affiliated Hospital, Peking University Health Science Center, Peking University, Beijing, China; Department of Biological Science and Biotechnology, Tsinghua University, Beijing, China; School of Oncology, Peking University Health Science Center, Peking University, Beijing, China.
Reference
1. Zhao, Y. et al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nature Cell Biol. doi:10.1038/ncb2069 (2010). | Article"