The expression of<i>beclin 1</i>is associated with favorable prognosis in stage IIIB colon cancers

Li, Bao Xiu; Li, Chun Yon; Peng, Rui; Wu, Xiao; Wang, Hai Ying; Wan, De Sen; Zhu, Xiao Feng; Zhang, Xiao Shi

doi:10.4161/auto.5.3.7491

Cited by 136 publications

(145 citation statements)

References 17 publications

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“…Experiments in vitro had reported that Beclin-1 could be as a reliable marker in monitoring the prognosis in CRC. However, conflicting results have been also reported from different laboratories (Guo et al, 2011;Li et al, 2009). In our meta-analysis, higher Beclin-1 expression was positively linked to tumor distant metastasis, which was also confirmed by Ahn's study (Ahn et al, 2007).…”

Section: Discussionmentioning

confidence: 73%

“…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.…”

Section: Introductionmentioning

confidence: 69%

“…Among them, 1 study was excluded because of the duplicated data about Beclin-1 expression. Finally, 6 articles were eligible for our present meta-analysis (Ahn Guo et al, 2011;Koukourakis et al, 2010;Li et al, 2009;Myung Park et al, 2013;Sui and Feng, 2012).…”

Section: Study Characteristicsmentioning

confidence: 99%

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

Han

Xue²,

Shen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 69%

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

Han

Xue²,

Shen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In human colon cancer tissue observed via immunohistochemistry, Beclin 1 is distributed within the plasmamembrane, the cytoplasm and the nucleus. 11 Beclin 1 contains three identified structural domains: a BH3 domain (amino acids 114-123) at the N-terminus, a central coiled-coil domain (CCD, amino acids 144-269) and an evolutionarily conserved domain (ECD, amino acids 244-337) (Figure 2a). The ECD is essential for Beclin 1's ability to mediate autophagy and to inhibit tumorigenesis.…”

Section: Beclin 1 Is a Bh3-only Domain Autophagy Proteinmentioning

confidence: 99%

The Beclin 1 network regulates autophagy and apoptosis

et al. 2011

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Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP 3 R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy. Cell Death and Differentiation (2011) 18, 571-580; doi:10.1038/cdd.2010 published online 11 February 2011 Autophagy is an essential process that consists of selective degradation of cellular components. There are at least three different types of autophagy described and possibly more. These autophagy types include macroautophagy (hereafter referred to as autophagy), microautophagy and chaperonemediated autophagy. 1 The initial step of autophagy is the surrounding and sequestering of cytoplasmic organelles and proteins within an isolation membrane (phagophore). Potential sources for the membrane to generate the phagophore include the Golgi complex, endosomes, the endoplasmic reticulum (ER), mitochondria and the plasma membrane. 2 The nascent membranes are fused at their edges to form double-membrane vesicles, called autophagosomes. Autophagosomes undergo a stepwise maturation process, including fusion with acidified endosomal and/or lysosomal vesicles, eventually leading to the delivery of cytoplasmic contents to lysosomal components, where they fuse, then degrade and are recycled (Figure 1a). The process of mammalian autophagy is divided into six principal steps: initiation (Figure 1b It has been well demonstrated that autophagy depends on Atg5/Atg7, is associated with microtubule-associated protein light chain 3 (LC3) truncation and lipidation, and may originate directly from the ER membrane and other membrane organelles. Furthermore, recent study has identified a Atg5/Atg7-independent pathway of autophagy. 3 This pathway of autophagy was not associated with LC3 processing but appeared to involve autophagosome formation from late endosomes and the trans-Golgi. 3 Atg7-independent autophagy had been implicated in mitochondrial clearance from reticulocytes. 4 The exact molecular basis of Atg5/Atg7-independent autophagy remains to be elucidated. Interestingly, Beclin 1 is required for Atg5/Atg7-dependent and -independent autophagy. 3 However, the presence of Beclin 1-indep...

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“…In addition, beclin-1 is a haploinsufficient tumor suppressor gene in mice, because loss of one beclin-1 allele in mice was shown to lead to a high incidence of lung and hepatocellular carcinomas, lymphomas, as well as mammary neoplastic lesions (30,31). Also importantly, decreased Beclin-1 expression was found to be strongly associated with reduced survival rate of stage IIIB colon cancer patients (32). Furthermore, increased Beclin-1 expression was demonstrated to block anchorage-independent growth and in vivo tumorigenicity of human breast carcinoma cells (33).…”

mentioning

confidence: 99%

Oncogenic ras-induced Down-regulation of Autophagy Mediator Beclin-1 Is Required for Malignant Transformation of Intestinal Epithelial Cells

Yoo

et al. 2010

Journal of Biological Chemistry

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Detachment of non-malignant epithelial cells from the extracellular matrix causes their growth arrest and, ultimately, death. By contrast, cells composing carcinomas, cancers of epithelial origin, can survive and proliferate without being attached to the extracellular matrix. These properties of tumor cells represent hallmarks of malignant transformation and are critical for cancer progression. Previously we identified several mechanisms by which ras, a major oncogene, blocks detachment-induced apoptosis of intestinal epithelial cells, but mechanisms by which Ras promotes proliferation of those cells that remain viable following detachment are unknown. We show here that detachment of non-malignant intestinal epithelial cells promotes formation of autophagosomes, vacuole-like structures that mediate autophagy (a process of cellular self-cannibalization), and that oncogenic ras prevents this autophagosome formation. We also found that ras activates a GTPase RhoA, that RhoA promotes activation of a protease calpain, and that calpain triggers degradation of Beclin-1, a critical mediator of autophagy, in these cells. The reversal of the effect of ras on Beclin-1 (achieved by expression of exogenous Beclin-1) promoted autophagosome formation following cell detachment, significantly reduced the fraction of detached cells in the S phase of the cell cycle and their rate of proliferation without affecting their viability. Furthermore, RNA interference-induced Beclin-1 down-regulation in non-malignant intestinal epithelial cells prevented detachmentdependent reduction of the fraction of these cells in the S phase of the cell cycle. Thus, ras oncogene promotes proliferation of those malignant intestinal epithelial cells that remain viable following detachment via a distinct novel mechanism that involves Ras-induced down-regulation of Beclin-1.The ability of cells that form carcinomas, cancers of epithelial origins, to survive and proliferate in the absence of adhesion to the extracellular matrix (ECM) 3 is thought to represent a critical prerequisite for carcinoma progression (1, 2). This concept is based on observations indicating that many types of normal epithelia grow in vivo as cellular monolayers in contact with a form of the ECM called basement membrane. Detachment from the ECM causes growth arrest (3) and apoptosis (4) of non-malignant epithelial cells (the latter type of death is referred to as anoikis (5)). By contrast, carcinomas typically represent three-dimensional disorganized multicellular masses in which the cells tend to be deprived of normal contacts with the basement membrane. It is known in this regard that carcinoma cells often secrete basement membrane degrading enzymes, and this allows tumors formed by these cells to invade adjacent tissues (6). Furthermore, at advanced stages of the disease cancer cells detach from the primary tumor and migrate toward ectopic locations, where they reattach and give rise to metastases (7,8). Despite the fact that carcinoma cells are frequently deprived of normal con...

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The expression ofbeclin 1is associated with favorable prognosis in stage IIIB colon cancers

Cited by 136 publications

References 17 publications

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

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

The Beclin 1 network regulates autophagy and apoptosis

Oncogenic ras-induced Down-regulation of Autophagy Mediator Beclin-1 Is Required for Malignant Transformation of Intestinal Epithelial Cells

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