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Downregulation of Beclin1 and Impairment of Autophagy in a Small Population of Colorectal Cancer

BACKGROUND: Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been ob...

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Detalles Bibliográficos
Autores principales: Chen, Zhihong, Li, Yanchun, Zhang, Chi, Yi, Hongmei, Wu, Chang, Wang, Junpu, Liu, Yuwu, Tan, Jieqiong, Wen, Jifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781302/
https://www.ncbi.nlm.nih.gov/pubmed/23812859
http://dx.doi.org/10.1007/s10620-013-2732-8
Descripción
Sumario:BACKGROUND: Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been observed in most colorectal cancer tissues. However, there is a small population of colorectal cancers with downregulation of Beclin 1. AIM: The purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulaion of Beclin 1. METHODS: LC3 protein, an autophagosome marker, was assessed by ICH and WB in colorectal cancers tissues. An anti-tumor effect of Beclin 1 was examined by introducing exogenous Beclin 1 in vitro. Colony formation assay, growth curves and mouse xenograft were analysed. RESULTS: Our results showed that LC3 was suppressed in the colorectal cancers (9.86 %) with downregulation of Beclin 1. Moreover, overexpression of Beclin 1 inhibited colorectal cancer cell growth and enhanced the rapamycin-induced antitumor effect in vitro. CONCLUSION: Downregulation of Beclin 1 and autophagy inhibition play an important role in a part of colorectal cancers. Activating autophagy or overexperssion of Beclin 1 may be an effective treatment for some colorectal cancers. Detection of expression profile of Beclin 1 in colorectal cancers could be a strategy for new diagnostic and therapeutic methods. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10620-013-2732-8) contains supplementary material, which is available to authorized users.