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Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703
Department of Chemistry, Tsinghua University, Beijing 100084, China
The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China
Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
* Authors to whom correspondence should be addressed.
Received: 6 April 2012; in revised form: 23 April 2012 / Accepted: 7 May 2012 / Published: 15 May 2012
Abstract: Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.
Keywords: Pokemon; anoikis; Bim; hepatoma
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Liu, K.; Liu, F.; Zhang, N.; Liu, S.; Jiang, Y. Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703. Int. J. Mol. Sci. 2012, 13, 5818-5831.
Liu K, Liu F, Zhang N, Liu S, Jiang Y. Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703. International Journal of Molecular Sciences. 2012; 13(5):5818-5831.
Liu, Kun; Liu, Feng; Zhang, Nannan; Liu, Shiying; Jiang, Yuyang. 2012. "Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703." Int. J. Mol. Sci. 13, no. 5: 5818-5831.