L.-L. Fu, Y. Yang and H.-L. Xu contributed equally to this work.
Identification of novel caspase/autophagy-related gene switch to cell fate decisions in breast cancers
Article first published online: 4 JAN 2013
© 2013 Blackwell Publishing Ltd
Volume 46, Issue 1, pages 67–75, February 2013
How to Cite
Fu, L.-L., Yang, Y., Xu, H.-L., Cheng, Y., Wen, X., Ouyang, L., Bao, J.-K., Wei, Y.-Q. and Liu, B. (2013), Identification of novel caspase/autophagy-related gene switch to cell fate decisions in breast cancers. Cell Proliferation, 46: 67–75. doi: 10.1111/cpr.12005
- Issue published online: 7 JAN 2013
- Article first published online: 4 JAN 2013
- Manuscript Revised: 24 AUG 2012
- Manuscript Accepted: 24 AUG 2012
- Manuscript Received: 20 JUN 2012
- Young teacher's fund of Sichuan University. Grant Number: 2010SCU11066
- the Science Foundation for Post Doctorate Research of China. Grant Number: 20110491725
- the Major State Basic Research Development Program of China. Grant Number: 2010cb529900
Caspases, a family of cysteine proteases with unique substrate specificities, contribute to apoptosis, whereas autophagy-related genes (ATGs) regulate cytoprotective autophagy or autophagic cell death in cancer. Accumulating evidence has recently revealed underlying mechanisms of apoptosis and autophagy; however, their intricate relationships still remain to be clarified. Identification of caspase/ATG switches between apoptosis and autophagy may address this problem.
Materials and methods
Identification of caspase/ATG switches was carried out using a series of elegant systems biology & bioinformatics approaches, such as network construction, hub protein identification, microarray analyses, targeted microRNA prediction and molecular docking.
We computationally constructed the global human network from several online databases and further modified it into the basic caspase/ATG network. On the basis of apoptotic or autophagic gene differential expressions, we identified three molecular switches [including androgen receptor, serine/threonine-protein kinase PAK-1 (PAK-1) and mitogen-activated protein kinase-3 (MAPK-3)] between certain caspases and ATGs in human breast carcinoma MCF-7 cells. Subsequently, we identified microRNAs (miRNAs) able to target androgen receptor, PAK-1 and MAPK-3, respectively. Ultimately, we screened a range of small molecule compounds from DrugBank, able to target the three above-mentioned molecular switches in breast cancer cells.
We have systematically identified novel caspase/ATG switches involved in miRNA regulation, and predicted targeted anti-cancer drugs. These findings may uncover intricate relationships between apoptosis and autophagy and thus provide further new clues towards possible cancer drug discovery.