Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications

Vela, Driton; Vela-Gaxha, Zana

doi:10.1038/emm.2017.273

Cited by 62 publications

(62 citation statements)

References 116 publications

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“…Dysregulation of the hepcidin-FPN axis has been associated with the development of cancer. This most likely results from higher rates of cell proliferation requiring greater demand for iron [63]. Thus, reduced hepatic hepcidin was found to offer a protective effect against the progression of lung [64] and breast cancer [65,66].…”

Section: Hepcidin/fpn Axis Dysregulationmentioning

confidence: 98%

Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis

et al. 2019

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The interaction between hepcidin and ferroportin is the key mechanism involved in regulation of systemic iron homeostasis. This axis can be affected by multiple stimuli including plasma iron levels, inflammation and erythropoietic demand. Genetic defects or prolonged inflammatory stimuli results in dysregulation of this axis, which can lead to several disorders including hereditary hemochromatosis and anaemia of chronic disease. An imbalance in iron homeostasis is increasingly being associated with worse disease outcomes in many clinical conditions including multiple cancers and neurological disorders. Currently, there are limited treatment options for regulating iron levels in patients and thus significant efforts are being made to uncover approaches to regulate hepcidin and ferroportin expression. These approaches either target these molecules directly or regulatory steps which mediate hepcidin or ferroportin expression. This review examines the current status of hepcidin and ferroportin agonists and antagonists, as well as inducers and inhibitors of these proteins and their regulatory pathways.

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Section: Hepcidin/fpn Axis Dysregulationmentioning

confidence: 98%

Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis

et al. 2019

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“…Similarly, resection of a hepcidin-producing hepatic adenoma in a patient suffering from refractory anemia leads to spontaneously reduction of anemia. Hepcidin expression was reported to be altered in various cancers [81]. This therefore suggests that hepcidin expression in a tumor cell microenvironment may initiate and/or accentuate tumorigenesis.…”

Section: Hepcidinmentioning

confidence: 99%

“…Previously, studies on in vivo iron homeostasis revealed that the expression of hepcidin in the liver is positively regulated by HJV, TfR2, HFE and BMP. Most of the BMP tested, including BMP2, 4, 5, 6 and 9, were reported to be strong inducers of hepcidin [81,83,84]. Interestingly, Furin acts also on the maturation of these BMPs, and on other class of TGF-β molecules [19].…”

Section: Hepcidinmentioning

confidence: 99%

Proprotein convertases: Key players in inflammation-related malignancies and metastasis

et al. 2020

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A B S T R A C TMany cancers occur from locations of inflammation due to chronic irritation and/or infection. Tumor microenvironment contains various different inflammatory cells and mediators that orchestrate diverse neoplastic processes, including proliferation, survival, adhesion and migration. In parallel, tumor cells have adapted some of the signaling molecules used by inflammatory cells, such as selectins and chemokines as well as their receptors for invasion, extravasation and subsequently metastasis. Expression and/or activation of the majority of these molecules is mediated by the proprotein convertases (PCs); proteases expressed by both tumor cells and inflammatory cells. This review analyzes the potential role of these enzymatic system in inflammation-associated cancer impacting on the malignant and metastatic potential of cancer cells, describing the possible use of PCs as a new anti-inflammatory therapeutic approach to tumor progression and metastasis.

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“…Furthermore, the gene expression profiles of around 800 breast cancer patients have reported that a decrease in ferroportin gene expression is correlated with an important reduction in metastasis-free and disease-free survival [35]. Numerous studies have shown that hepcidin contributes to cancer proliferation and progression, then regulating its level to reduce iron pool in tumor cells may be a new strategy in cancer treatment [36].…”

Section: Relationship Between Iron Metabolism and Cancermentioning

confidence: 99%

Iron Metabolism in Cancer Progression

Forciniti

Greco

Grizzi

et al. 2020

IJMS

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Iron is indispensable for cell metabolism of both normal and cancer cells. In the latter, several disruptions of its metabolism occur at the steps of tumor initiation, progression and metastasis. Noticeably, cancer cells require a large amount of iron, and exhibit a strong dependence on it for their proliferation. Numerous iron metabolism-related proteins and signaling pathways are altered by iron in malignancies, displaying the pivotal role of iron in cancer. Iron homeostasis is regulated at several levels, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Mutations in HFE gene alter iron homeostasis leading to hereditary hemochromatosis and to an increased cancer risk because the accumulation of iron induces oxidative DNA damage and free radical activity. Additionally, the iron capability to modulate immune responses is pivotal in cancer progression. Macrophages show an iron release phenotype and potentially deliver iron to cancer cells, resulting in tumor promotion. Overall, alterations in iron metabolism are among the metabolic and immunological hallmarks of cancer, and further studies are required to dissect how perturbations of this element relate to tumor development and progression.

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Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications

Cited by 62 publications

References 116 publications

Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis

Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis

Proprotein convertases: Key players in inflammation-related malignancies and metastasis

Iron Metabolism in Cancer Progression

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