BNIP3 promotes HIF‐1α‐driven melanoma growth by curbing intracellular iron homeostasis

Vara-Pérez, Mónica; Rossi, Matteo; Haute, Chris Van den; Maes, Hannelore; Sassano, Maria Livia; Venkataramani, Vivek; Michalke, Bernhard; Romano, Erminia; Rillaerts, Kristine; Garg, Abhishek D.; Schepkens, Corentin; Bosisio, Francesca Maria; Wouters, Jasper; Oliveira, Ana I.; Vangheluwe, Peter; Annaert, Wim; Swinnen, Johannes V.; Colet, Jean Marie; Oord, Joost J. van den; Fendt, Sarah-Maria; Mazzone, Massimiliano; Agostinis, Patrizia

doi:10.15252/embj.2020106214

Cited by 47 publications

(28 citation statements)

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“…Both the increase in Fe(II), together with constant total Fe, underlines the necessity to monitor the concentrations of the redox couple Fe(II)/Fe(III), instead of total iron, when investigating molecular mechanisms in OS-related pathologies, as shown in subsequent Figure 3 . In this paper, BNIP3-melanoma cells display increased intracellular Fe(II) levels, caused by an elevated, NCOA4-mediated ferritinophagy, the latter fostering PHD2-mediated HIF-1α destabilization [ 76 ].…”

Section: Iron Redox Speciationmentioning

confidence: 99%

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Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

Michalke

2022

IJMS

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Element analysis in clinical or biological samples is important due to the essential role in clinical diagnostics, drug development, and drug-effect monitoring. Particularly, the specific forms of element binding, actual redox state, or their spatial distribution in tissue or in single cells are of interest in medical research. This review summarized exciting combinations of sophisticated sample delivery systems hyphenated to inductively coupled plasma-mass spectrometry (ICP-MS), enabling a broadening of information beyond the well-established outstanding detection capability. Deeper insights into pathological disease processes or intracellular distribution of active substances were provided, enabling a better understanding of biological processes and their dynamics. Examples were presented from spatial elemental mapping in tissue, cells, or spheroids, also considering elemental tagging. The use of natural or artificial tags for drug monitoring was shown. In the context of oxidative stress and ferroptosis iron, redox speciation gained importance. Quantification methods for Fe2+, Fe3+, and ferritin-bound iron were introduced. In Wilson’s disease, free and exchangeable copper play decisive roles; the respective paragraph provided information about hyphenated Cu speciation techniques, which provide their fast and reliable quantification. Finally, single cell ICP-MS provides highly valuable information on cell-to-cell variance, insights into uptake of metal-containing drugs, and their accumulation and release on the single-cell level.

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Section: Iron Redox Speciationmentioning

confidence: 99%

“…The data are analyzed using a one-way ANOVA with Tukey’s multiple comparisons test. ** p < 0.01 shBNIP3 compared against shCntl, ## p < 0.01 shBNIP3 compared against shATG5.Reprinted, [ 76 ]. Copy right year: 2021, copyright owner: John Wiley and Sons.…”

Section: Figurementioning

confidence: 99%

Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

Michalke

2022

IJMS

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“…The expression of NCOA4 is lower in Clear cell renal cell carcinoma (ccRCC) tissues compared with normal tissues, and low NCOA4 expression is closely related to high-grade malignant tumors and advanced TNM staging (165,166). Some studies have indicated the critical role of NCOA4mediated ferritinophagy in tumor progression, such as knockdown of COPZ1 leads to an increase in NCOA4, resulting in the degradation of ferritin, and ultimately ferroptosis in glioblastoma ( 167 melanoma cells lacking BNIP3 showed increased intracellular iron levels caused by NCOA4-mediated increase in ferritinophagy (168). Nevertheless, NCOA4-mediated ferritinophagy is not effective in all tumors as Hasan et al found that the destruction of ferritinophagy by NCOA4 knockout resulted in minor differences in growth under basal and iron-restricted conditions in colon cancer cells; Additionally, NCOA4 does not engage in cell death induced by 5-fluorouracil and erastin (169).…”

Section: Iron and Ferritinophagymentioning

confidence: 99%

“…Some studies have indicated the critical role of NCOA4-mediated ferritinophagy in tumor progression, such as knockdown of COPZ1 leads to an increase in NCOA4, resulting in the degradation of ferritin, and ultimately ferroptosis in glioblastoma ( 167 ); Vara-Pérez et al. found that melanoma cells lacking BNIP3 showed increased intracellular iron levels caused by NCOA4-mediated increase in ferritinophagy ( 168 ). Nevertheless, NCOA4-mediated ferritinophagy is not effective in all tumors as Hasan et al.…”

Section: Iron and Cell Deathmentioning

confidence: 99%

The Role of Iron in Cancer Progression

et al. 2021

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Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. In addition, iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. Here, we reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors.

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“…BCL2 19 kD protein-interacting protein 3 (BNIP3) is a mitochondrial protein belonging to the BCL-2 family, which has been demonstrated to be involved in the complex regulation of cell death, autophagy and cellular protection [ 219 , 220 ]. Regulation of BNIP3 levels has been implicated in different types of neoplasias, namely, breast cancer [ 221 ], lung cancer [ 222 ], salivary adenoid cystic carcinoma [ 223 ] and skin melanoma [ 224 ], being associated with progression of the disease and prognosis. In a recent study, the expression of BNIP3 was evaluated through IHC in a cohort of 47 primary UM cases and the authors demonstrated that higher levels of BNIP3 were correlated with a shorter survival [ 189 ].…”

Section: Immunohistochemistry-based Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

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BNIP3 promotes HIF‐1α‐driven melanoma growth by curbing intracellular iron homeostasis

Cited by 47 publications

References 47 publications

Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

The Role of Iron in Cancer Progression

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

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