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

Abstract

BackgroundAutophagy 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.AimThe purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulaion of Beclin 1.MethodsLC3 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.ResultsOur 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.ConclusionDownregulation 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 materialThe online version of this article (doi:10.1007/s10620-013-2732-8) contains supplementary material, which is available to authorized users.

Intestinal Autophagy and Its Pharmacological Control in Inflammatory Bowel Disease

“…It was previously reported that overexpression of Beclin-1 in vitro inhibited CRC cells growth and enhanced the rapamycin-induced antitumor effects (136). Patients with high levels of Beclin-1 presented good prognosis and longer survival (131, 135), and ATG10 downregulation was associated with cell migration and invasion of CRC cells (137).…”

“…Some evidence has shown that autophagy is highly induced in most CRC patients and CRC cells (130–135). However, there is also a small population of CRC patients with downregulated autophagy (136). Based on those reports, the expression profile of autophagy is inconsistent in CRC patients.…”

New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets

“…In CRC tissues, BECN1 can be either up- or downregulated 184 . The activation of autophagy by overexpressing BECN1 may be an effective treatment of CRC with defects in BECN1 186 . In one study, the expression and significance of 3 autophagy-related proteins, namely BECN1, LC3, and MTOR, were investigated in the tumorigenesis and development of CRC.…”

Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis

“…Similar studies also demonstrated that over-expression of Beclin-1 inhabited colorectal cancer cell growth (Chen et al, 2013), and the higher level of Beclin-1 was strongly associated with longer survival (Li et al, 2009). So no certainty outcomes were determined up to now.…”

“…The autophagic cancer cell response to ionizing radiation and chemotherapy seems to affect the efficacy of chemotherapy and radiotherapy (Zois and (Chen et al, 2013;Zhang et al, 2013). Though oncogenes and tumor suppressor genes are also involved in the regulation of autophagy, the role of autophagy in the metastasis and prognosis of human colorectal cancer are still poorly understood (Maiuri et al, 2009).…”