Autophagy and Bcl‐2/BNIP3 death regulatory pathway in non‐small cell lung carcinomas

Karpathiou, Georgia; Sivridis, Efthimios; Koukourakis, Michael I.; Mikroulis, Dimitrios; Bouros, Demosthenes; Froudarakis, Marios; Bougioukas, Georgios; Maltezos, Efstratios; Giatromanolaki, Alexandra

doi:10.1111/apm.12026

Cited by 24 publications

(16 citation statements)

References 55 publications

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“…The total study sample size of 54 studies was 8522 with a mean of 158 (range, 45-535 patients). 23 cohorts (Pezzella et al, 1993;Fontanini et al, 1995;Fontanini et al, 1996;O'Neill et al, 1996;Apolinario et al, 1997;Koukourakis et al, 1997;Pastorino et al, 1997;Fontanini et al, 1998;Cox et al, 2000;Moldvay et al, 2000;Nguyen et al, 2000;Cox et al, 2001;Laudanski et al, 2001;Rigau et al, 2002;Swinson et al, 2002;Grossi et al, 2003;Swinson et al, 2004;Fokkema et al, 2006;Yaren et al, 2006;Ludovini et al, 2008;Anagnostou et al, 2010;Grimminger et al, 2010;Karpathiou et al, 2013) evaluated patients from Europe, 12 cohorts (Ritter et al, 1995;Anton et al, 1997;Kwiatkowski et al, 1998;D'Amico et al, 1999;Mehdi et al, 1999;Carvalho et al, 2000;Han et al, 2002;Huang et al, 2003;Poleri et al, 2003;Renouf et al, 2009;Anagnostou et al, 2010;Graziano et al, 2010) from America and 21 cohorts (Ohsaki et al, 1996;Higashiyama et al, 1997;…”

Section: Study Selection and Quality Assessmentmentioning

confidence: 99%

High Expression of Bcl-2 Protein Predicts Favorable Outcome in Non-small Cell Lung Cancer: Evidence from a Systematic Review and Meta-analysis

Zhao

He²,

Gao³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: The prognostic value of Bcl-2 protein expression in non-small cell lung cancer (NSCLC) is under debate. We therefore systematically reviewed the evidence for Bcl-2 protein effects on NSCLC survival to elucidate this issue. Materials and Methods: An electronic search in Pubmed and Embase complemented by manual searches in article references were conducted to identify eligible studies to evaluate the association between Bcl-2 protein expression and overall survival (OS) as well as disease free survival (DFS) of NSCLC patients. Combined hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were pooled using the random-effects model.

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Section: Study Selection and Quality Assessmentmentioning

confidence: 99%

High Expression of Bcl-2 Protein Predicts Favorable Outcome in Non-small Cell Lung Cancer: Evidence from a Systematic Review and Meta-analysis

Zhao

He²,

Gao³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The process is precisely regulated by ATG proteins, among which Beclin 1 is a major regulator in autophagy initiation and shown to be involved in several other biological functions in human diseases, including heart disease (Essick et al, 2013;Zeng et al, 2013), cancer (Jiang et al, 2012;Han et al, 2013;Karpathiou et al, 2013;Wu et al, 2013;Yu et al, 2013), pathogen infection (Liu et al, 2005;Patel et al, 2008;Huang et al, 2009;Vazquez et al, 2010), and neurodegeneration (Xing et al, 2012;Fields et al, 2013;Lucin et al, 2013;Nascimento-Ferreira et al, 2013). Beclin 1-/-mice die early in embryogenesis and Beclin 1+/-mice suffer from a high incidence of spontaneous tumors, including B-lymphoblast cell lymphoma (Yue et al, 2003), an aggressive disease characterized by excessive proliferation of immature B cells in lymphoid tissues.…”

Section: Introductionmentioning

confidence: 99%

Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells

Niu¹,

Liu²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Beclin 1 is a key factor for initiation and regulation of autophagy, which is a cellular catabolic process involved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagy in leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cells from 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. New transcript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletion of exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform was assessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variable transcript is generated by alternative 3' splicing, and its translational product displayed a reduced activity in induction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negative in leukemogenesis regulated by autophagy.

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“…Previous studies show that BNIP3 overexpression enhances tumor growth in lung cancer xenografts and correlates with poor survival in lung cancer patients. 38,39 BNIP3's contribution to tumorigenesis has yet to be linked to its role in mitophagy; however, the fact that increased levels of BNIP3 are associated with more aggressive disease suggests that a function in tumor cell survival via autophagy or mitophagy is a more likely mechanistic scenario than a role in cell death, in contexts of BNIP3 overexpression. Autophagy has documented roles in KRAS-driven lung 27,28 and pancreatic 40,41 cancer progression, and overactive RAS has been shown to upregulate BNIP3.…”

mentioning

confidence: 99%

Cross-cancer profiling of molecular alterations within the human autophagy interaction network

et al. 2015

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Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumorrelated alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival.

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Autophagy and Bcl‐2/BNIP3 death regulatory pathway in non‐small cell lung carcinomas

Cited by 24 publications

References 55 publications

High Expression of Bcl-2 Protein Predicts Favorable Outcome in Non-small Cell Lung Cancer: Evidence from a Systematic Review and Meta-analysis

High Expression of Bcl-2 Protein Predicts Favorable Outcome in Non-small Cell Lung Cancer: Evidence from a Systematic Review and Meta-analysis

Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells

Cross-cancer profiling of molecular alterations within the human autophagy interaction network

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