The prohibitin-binding compound fluorizoline inhibits mitophagy in cancer cells

Núñez-Vázquez, Sonia; Saura-Esteller, José; Sánchez-Vera, Ismael; Guilbaud, Emma; Cosialls, Ana M.; Pons, Gabriel; Ricci, Jean-Ehrland; Iglesias-Serret, Daniel; Marchetti, Sandrine; Gil, Joan

doi:10.1038/s41389-021-00352-9

Cited by 14 publications

(4 citation statements)

References 46 publications

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“…There are two publications that support this observation. Two PHB2 specific modulators, rocaglamide [ 72 ] and fluorizoline [ 41 , 42 ], bind to PHB2 and inhibit protein translation. (1) Rocaglamide inhibits the Ras-Raf-MEK-ERK signaling pathway, suppressing Mnk-1-dependent phosphorylation of the translation initiation factor, eIF4E, which plays a crucial role in cap-dependent protein translation [ 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another paper reported a controversial oncogenic function of PHB2 in MCF7 (a breast cancer cell line with estrogen, progesterone, and glucocorticoid receptors) cells [ 40 ]. Fluorizolines, a PHB1/2 specific modulator [ 41 , 42 ], interrupt the interaction between PHB2 and γ-glutamylcyclotransferases (GGCT) and enhance p21 expression. Fluorizoline treatment prevents PHB2’s translocation into the nucleus and inhibits cell cycle progression.…”

Section: Phb2 Tumor Suppressor Functionmentioning

confidence: 99%

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Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer

Lamont

Liu

et al. 2023

Cells

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Prohibitins (PHBs) are a highly conserved class of proteins and have an essential role in transcription, epigenetic regulation, nuclear signaling, mitochondrial structural integrity, cell division, and cellular membrane metabolism. Prohibitins form a heterodimeric complex, consisting of two proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2). They have been discovered to have crucial roles in regulating cancer and other metabolic diseases, functioning both together and independently. As there have been many previously published reviews on PHB1, this review focuses on the lesser studied prohibitin, PHB2. The role of PHB2 in cancer is controversial. In most human cancers, overexpressed PHB2 enhances tumor progression, while in some cancers, it suppresses tumor progression. In this review, we focus on (1) the history, family, and structure of prohibitins, (2) the essential location-dependent functions of PHB2, (3) dysfunction in cancer, and (4) the promising modulators to target PHB2. At the end, we discuss future directions and the clinical significance of this common essential gene in cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Phb2 Tumor Suppressor Functionmentioning

confidence: 99%

Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer

Lamont

Liu

et al. 2023

Cells

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“…In lung or pancreatic cancer cells, the loss of the mitophagic proteins ATG7 or ATG5 significantly decreases the aggressiveness of the tumor due to the accumulation of defective mitochondria and an excessive accumulation of lipids, accounting for a greater alteration in the ß-oxidation of fatty acids [155]. Anti-tumorigenic Colorectal cancer cell, melanoma, and squamous cell carcinoma [167] FKBP8 Pro-tumorigenic Hepatocellular Carcinoma [168] Anti-tumorigenic Schwannoma, melanoma [169] NLRX1 Pro-tumorigenic Breast [170] Anti-tumorigenic Pancreatic [171] Prohibitin-2 Pro-tumorigenic Lung, Cervical [172,173] cell carcinomas, three esophagus cancer cell lines, three prostate cancer cell lines, and six colon cancer cell lines, and FAM162A, BNIP3, and NIX genes were overexpressed [183,184].…”

Section: Mitophagic Gene Signaturementioning

confidence: 99%

Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space

Cabané,

Correa,

Bode

et al. 2024

IJMS

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Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments. Despite the availability of commercial molecular tests, their widespread use has been hindered in our experience due to cost constraints and variability between them. Thus, numerous groups are currently evaluating new molecular markers that ultimately will lead to improved diagnostic certainty, as well as better classification of prognosis and recurrence. In this review, we start reviewing the current preoperative testing methodologies, followed by a comprehensive review of emerging molecular markers. We focus on micro RNAs, long non-coding RNAs, and mitochondrial (mt) signatures, including mtDNA genes and circulating cell-free mtDNA. We envision that a robust set of molecular markers will complement the national and international clinical guides for proper assessment of the disease.

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“…Depletion of ATG5 reduced tumor growth in RAS mutation lung cancer cell line [11]. Pro-apoptotic compound fluorizoline was identified to inhibit PRKN-dependent mitophagy and lower the viability of lung cancer cell line [12]. However, there was no comprehensive genetic and transcriptional analysis of all key mitophagy genes in LUAD progression, prognosis and therapeutics.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Analysis of the Effects of Key Mitophagy Genes on the Progression and Prognosis of Lung Adenocarcinoma

Dai

Guo

Shui

et al. 2022

Cancers

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The aim of our study was to perform a comprehensive analysis of the gene expression, copy number variation (CNV) and mutation of key mitophagy genes in the progression and prognosis of lung adenocarcinoma (LUAD). We obtained the data from The Cancer Genome Atlas (TCGA). Clustering analysis was performed to stratify the mitophagy related groups. The least absolute shrinkage and selection operator (LASSO) based cox model was used to select hub survival genes. An independent validation cohort was retrieved from Gene Expression Omnibus database. We found 24 out of 27 mitophagy genes were aberrantly expressed between tumor and normal samples. CNV gains were associated with higher expression of mitophagy genes in 23 of 27 mitophagy genes. The clustering analysis identified high and low risk mitophagy groups with distinct survival differences. The high risk mitophagy groups had higher tumor mutation burden, stemness phenotype, total CNVs and lower CD4+ T cells infiltration. Drugs targeted to high risk mitophagy groups were identified including the PI3K/AKT/mTOR inhibitor, HDAC inhibitor and chemotherapy agents such as cisplatin and gemcitabine. In addition, the differentially expressed genes (DEGs) were identified between mitophagy groups. Further univariate Cox analysis of each DEG and subsequent LASSO-based Cox model revealed a mitophagy-related prognostic signature. The risk score model of this signature showed a strong ability to predict the overall survival of LUAD patients in training and validation datasets. In conclusion, the mitophagy genes played an important role in the progression and prognosis of LUAD, which might provide useful information for the treatment of LUAD.

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The prohibitin-binding compound fluorizoline inhibits mitophagy in cancer cells

Cited by 14 publications

References 46 publications

Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer

Essential Protein PHB2 and Its Regulatory Mechanisms in Cancer

Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space

A Comprehensive Analysis of the Effects of Key Mitophagy Genes on the Progression and Prognosis of Lung Adenocarcinoma

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