4.4 Article

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

Journal

DIGESTIVE DISEASES AND SCIENCES
Volume 58, Issue 10, Pages 2887-2894

Publisher

SPRINGER
DOI: 10.1007/s10620-013-2732-8

Keywords

Colorectal cancer; Beclin 1; Autophagy; Rapamycin

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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.

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