Autophagy as a cytoprotective mechanism in esophageal squamous cell carcinoma

Hall, Timothy M.; Tétreault, Marie Pier; Hamilton, Kathryn E.; Whelan, Kelly A.

doi:10.1016/j.coph.2018.04.003

Cited by 23 publications

(21 citation statements)

References 56 publications

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“…On the other hand, constitutive autophagy is often associated with tumor progression and poor survival outcomes in human cancers, including pancreatic cancer, 111 colorectal cancer (CRC), 112 gliomas, 113 and esophageal cancer. 114 Cancer cells are strongly adaptive in response to environmental insults, and thus the metabolic alterations characteristic to autophagy contribute to a phenomenon called “austerity,” or a tolerance to nutrient deprivation. 43,112 Tumors that exhibit resistance to uneven perfusion and poor nutritive blood flow in the tumor environment, like pancreatic tumors, benefit from autophagy-mediated upkeep of metabolites, whereas reversal of austerity can be achieved via artificial repression of autophagy, leading to resensitivity to starvation and subsequent cell death 43 .…”

Section: The Two Faces Of Autophagymentioning

confidence: 99%

A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics

Wang

Bonavida

2018

Crit Rev Oncog

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The complexities of molecular signaling in cancer cells have been hypothesized to mediate cross-network alterations of oncogenic processes such as uncontrolled cell growth, proliferation, acquisition of epithelial-to-mesenchymal transition (EMT) markers, and resistance to cytotoxic therapies. The two biochemically exclusive processes/proteins examined in the present review are the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP) and the cell-intrinsic system of macroautophagy (hereafter referred to as autophagy). RKIP is poorly expressed in human cancer tissues, and low expression levels are correlated with high incidence of tumor growth, metastasis, poor treatment efficacy, and poor prognoses in cancer patients. By comparison, autophagy is a conserved cytoprotective degradation pathway that has been shown to influence the acquisition of resistance to hypoxia and nutrient depletion as well as the regulation of chemoimmuno-resistance and apoptotic evasion. Evidently, a broad library of cancer-relevant studies exists for RKIP and autophagy, although reports of the interactions between pathways involving RKIP and autophagy have been relatively sparse. To circumvent this limitation, the coordinate regulatory and effector mechanisms were examined for both RKIP and autophagy. Here, we propose three putative pathways that demonstrate the inherent pleiotropism and relevance of RKIP and the microtubule-associated protein 1 light chain 3 (MAP1LC3, LC3) on cell growth, proliferation, senescence, and EMT, among the hallmarks of cancer. Our findings suggest that signaling modules involving p53, signal transducer and activator of transcription 3 (STAT3), nuclear factor-κB (NF-κB), and Snail highlight the novel roles for RKIP in the control of autophagy and vice versa. The suggested potential crosstalk mechanisms are new areas of research in which to further study RKIP and autophagy in cancer models. These should lead to novel prognostic motifs and will provide alternative therapeutic strategies for the treatment of unresponsive aggressive cancer types.

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Section: The Two Faces Of Autophagymentioning

confidence: 99%

A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics

Wang

Bonavida

2018

Crit Rev Oncog

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“…It degrades and removes damaged organelle components in cells to maintain the homeostasis of cells and provides nutritional support for cell survival [5]. Previous studies have found that abnormal autophagy is associated with a variety of human diseases such as Alzheimer's disease, cardiovascular disease, and several types of cancer including ESCC [6][7][8]. As the first autophagy-specific gene identified, Beclin-1 plays an important role in the regulation of autophagy.…”

Section: Introductionmentioning

confidence: 99%

Beclin-1 is a Promising Prognostic Biomarker in a Specific Esophageal Squamous Cell Carcinoma Population

Luo

Shi

et al. 2021

Pathol. Oncol. Res.

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The effects of autophagy and apoptosis in the prognostic assessment and treatment of Esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Here, we conducted a retrospective study on the histopathology of ESCC, investigated the expression of Beclin-1 and Bcl-2 proteins (both autophagy- and apoptosis-related) in esophageal cancer tissue, and analyzed the significance of these proteins for the prognosis of ESCC. In the present study, the expression level of Beclin-1 in ESCC was significantly lower than that in adjacent tissues (p < 0.01), whereas the expression level of Bcl-2 showed the opposite pattern (p < 0.01). Furthermore, low expression of Beclin-1 was associated with more advanced ESCC stages and lymph node metastasis. However, high expression of Bcl-2 was associated with more advanced ESCC stages, deeper tumor invasion, and lymph node metastasis. Moreover, the relationship between Bcl-2 expression and OS was not significant (p > 0.05), whereas Beclin-1 expression was significantly associated with OS (p < 0.05). Subgroup analysis showed that Beclin-1 expression was significantly associated with OS in the high-Bcl-2-expression group but not in the low-Bcl-2-expression group. Importantly, Beclin-1 upregulation or downregulation significantly upregulated or downregulated invasion, respectively, in EC9706 cells in combination with high expression but not low expression of Bcl-2. These findings reveal that differences in autophagy and apoptotic states and their activities may promote malignant tumor differentiation, which could lead to a more aggressive esophageal squamous cell phenotype and a worse survival prognosis. Here, Beclin-1 was shown to be a promising prognostic biomarker and therapeutic target for patients with ESCC in the high-Bcl-2-expression population.

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“…In the early stage of ESCA, autophagy can activate anti-tumor cells and micro-environment to inhibit the development of ESCA [16]. However, in the middle and later stages of ESCA, autophagy can be used as a promoter of tumor development, by clearing abnormal mitochondria and providing energy for tumor cells, and then promote the proliferation and metastasis of tumor cells [17]. Whelan et al have also demonstrated that autophagy can promote the metastasis of ESCA by mediating the mechanism of epithelial-mesenchymal transition (EMT) [18].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, cancer can change the normal autophagy mechanism, and autophagy-related gene mutations can lead to the occurrence of cancer [5].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics analysis of autophagy-related lncRNAs in esophageal carcinoma

Ding

Fan

2020

Preprint

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Background: Esophageal carcinoma (ESCA) is a malignant tumor with high invasiveness and mortality. Autophagy has multiple roles in the development of cancer; however, there are limited data on autophagy genes associated with long non-coding RNAs (lncRNAs) in ESCA. The purpose of this study was to screen potential diagnostic and prognostic molecules, and to identify gene co-expression networks associated with autophagy in ESCA. Methods: We downloaded transcriptome expression profiles from The Cancer Genome Atlas and autophagy-related gene data from the Human Autophagy Database, and analyzed the co-expression of mRNAs and lncRNAs. In addition, the diagnostic and prognostic value of autophagy-related lncRNAs was analyzed by multivariate Cox regression. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was carried out for high-risk patients, and enriched pathways were analyzed by gene set enrichment analysis. Results: The results showed that genes of high-risk patients were enriched in protein export and spliceosome. Based on Cox stepwise regression and survival analysis, we identified seven autophagy-related lncRNAs with prognostic and diagnostic value, with the potential to be used as a combination to predict the prognosis of patients with ESCA. Finally, a co-expression network related to autophagy was constructed. Conclusion: These results suggest that autophagy-related lncRNAs and the spliceosome play important parts in the pathogenesis of ESCA. Our findings provide new insight into the molecular mechanism of ESCA and suggest a new method for improving its treatment.

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Autophagy as a cytoprotective mechanism in esophageal squamous cell carcinoma

Cited by 23 publications

References 56 publications

A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics

A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics

Beclin-1 is a Promising Prognostic Biomarker in a Specific Esophageal Squamous Cell Carcinoma Population

Bioinformatics analysis of autophagy-related lncRNAs in esophageal carcinoma

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