Peroxisomes and cancer: The role of a metabolic specialist in a disease of aberrant metabolism

Dahabieh, Michael; Pietro, Erminia Di; Jangal, Maïka; Gonçalves, Christophe; Witcher, Michael; Braverman, Nancy; Rincón, Sonia V. del

doi:10.1016/j.bbcan.2018.07.004

Cited by 73 publications

(69 citation statements)

References 213 publications

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“…Reprogramming of metabolic pathways are implicated in the process of tumor development to facilize its unregulated growth and metastatic dissemination (Hanahan and Weinberg, 2011). Recently, the involvement of peroxisome pathway in cancer was demonstrated (Dahabieh et al, 2018). However, although dysfunctions of peroxisomes were shown in many tumors (De Craemer, 1995;Valenca et al, 2015), their roles in lung cancer were rarely explored.…”

Section: Discussionmentioning

confidence: 99%

“…Metabolic reprogramming is one of the core traits of the cancer cells, due to the multiple alterations during the multi-step process of tumorigenesis (Soga, 2013;El Hassouni et al, 2019). In recent years, with the deepening understanding of the important functions of the peroxisomes, more and more attention were paid to the peroxisomes research (Tanner et al, 2013;El Hassouni et al, 2019) and they were demonstrated to be implicated in innate immunity (Ferreira et al, 2019), signal transduction (Schrul and Schliebs, 2018), aging (Deori et al, 2018), and cancer (Dahabieh et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

et al. 2020

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To explore the potential functions and clinical significances of peroxisomes during lung cancer development and progression, we investigated the expressional profiles of peroxisome pathway genes and their correlations with clinical features in nonsmall cell lung cancer (NSCLC). The RNA-seq data of NSCLC including lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with their clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene expression comparisons between tumor and normal samples were performed with edgeR package in R software and the results of the 83 peroxisome pathway genes were extracted. Through Venn diagram analysis, 38 common differentially expressed peroxisome pathway genes (C-DEPGs) in NSCLC were identified. Principal components analysis (PCA) was performed and the 38 C-DEPGs could discriminate NSCLC tumors from the non-tumor controls well. Through Kaplan-Meier survival and Cox regression analyses, 11 of the C-DEPGs were shown to have prognostic effects on NSCLC overall survival (OS) and were considered as key C-DEPGs (K-DEPGs). Through Oncomine, Human Protein Atlas (HPA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), three K-DEPGs (HSD17B4, ACAA1, and PXMP4) were confirmed to be down-regulated in NSCLC at both mRNA and protein level. Their dyregulation mechanisms were revealed through their correlations with their copy number variations and methylation status. Their potential functions in NSCLC were explored through their NSCLC-specific co-expression network analysis, their correlations with immune infiltrations, immunomodulator gene expressions, MKI67 expression and their associations with anti-cancer drug sensitivity. Our findings suggested that HSD17B4, ACAA1, and PXMP4 might be new markers for NSCLC diagnosis and prognosis and might provide new clues for NSCLC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

et al. 2020

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“…Пероксины (факторы биогенеза пероксисом) представляют собой белки, необходимые для сборки функциональных пероксисом. Повышенная активность пероксисомальных ферментов обнаружена во многих типах опухолей [29]. На клетках гепатокарциномы человека разных линий показано, что ингибирование PEX2, PEX5, PEX10 и PEX12 малыми интерферирующими РНК останавливает рост клеток [23].…”

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Features of Redox Regulation in Tumor Cells

2019

SSMJ

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“…For this reason, T‐514 was renamed as peroxisomicine A1 (PA1). Peroxisomes play an active role in cancer development (for a review, see Dahabieh et al, 2018), and a hypothesis exists (Moreno‐Sepúlveda et al, 1997) that, as PA1 attacks peroxisomes, cells with fewer peroxisomes such as tumor cells from a significant number of neoplastic tissues (reviewed by Islinger et al, 2018), would be destroyed more easily than normal cells.…”

Section: Introductionmentioning

confidence: 99%

Peroxisomicine A1, a potential antineoplastic agent, causes micropexophagy in addition to macropexophagy

Ortega‐Martínez

Gutiérrez‐Dávila

Niderhauser‐García

et al. 2020

Cell Biology International

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Peroxisomicine A1 (PA1) is a potential antineoplastic agent with high and selective toxicity toward peroxisomes of tumor cells. Pexophagy is a selective autophagy process that degrades damaged peroxisomes; this process has been studied mainly in methylotrophic yeasts. There are two main modes of pexophagy in yeast: macropexophagy and micropexophagy. Previous studies showed that peroxisomes damaged by a prolonged exposition to PA1 are eliminated by macropexophagy. In this work, Candida boidinii was grown in methanol‐containing media, and PA1 was added to the cultures at 2 µg/mL after they reached the mid‐exponential growth phase. Samples were taken at 5, 10, 15, 20, and 25 min after the addition of PA1 and processed for ultrastructural analysis. Typical morphological characteristics of micropexophagy were observed: the direct engulfment of peroxisomes by the vacuolar membrane and the presence of the micropexophagic membrane apparatus (MIPA), which mediates the fusion between the opposing tips of the vacuole to complete sequestration of peroxisomes from the cytosol. In conclusion, here we report that, in addition to macropexophagy, peroxisomes damaged by PA1 can be eliminated by micropexophagy. This information is useful to deepen the knowledge of the mechanism of action of PA1 and of that of pexophagy per se.

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Peroxisomes and cancer: The role of a metabolic specialist in a disease of aberrant metabolism

Cited by 73 publications

References 213 publications

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

Features of Redox Regulation in Tumor Cells

Peroxisomicine A1, a potential antineoplastic agent, causes micropexophagy in addition to macropexophagy

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