New highlight in breast cancer development: the key role of hepcidin and iron metabolism

Scimeca, Manuel; Bonanno, Elena

doi:10.21037/atm.2018.10.30

Cited by 10 publications

(12 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is noteworthy that bone morphogenic proteins (BMPs), a class of transforming growth factor β ligands whose upregulation has been reported in various cancers, including breast, prostate, and bladder cancers, also induce hepcidin secretion by cancer cells [138]. Consistently, circulating plasma hepcidin is typically high and correlates with disease stage of 28 in breast, non-small lung, urothelial, and renal cancers [139][140][141][142][143]. Elevated serum ferritin has also been reported in many types of cancer, including neuroblastomas, lymphomas, colorectal, cervical, and breast cancers, and has been used as both a diagnostic tool and a prognostic factor [144][145][146][147][148][149].…”

Section: Systemic Iron Alterations In Cancermentioning

confidence: 97%

Iron: An Essential Element of Cancer Metabolism

Hsu

Mina

Roetto

et al. 2020

Cells

View full text Add to dashboard Cite

Cancer cells undergo considerable metabolic changes to foster uncontrolled proliferation in a hostile environment characterized by nutrient deprivation, poor vascularization and immune infiltration. While metabolic reprogramming has been recognized as a hallmark of cancer, the role of micronutrients in shaping these adaptations remains scarcely investigated. In particular, the broad electron-transferring abilities of iron make it a versatile cofactor that is involved in a myriad of biochemical reactions vital to cellular homeostasis, including cell respiration and DNA replication. In cancer patients, systemic iron metabolism is commonly altered. Moreover, cancer cells deploy diverse mechanisms to increase iron bioavailability to fuel tumor growth. Although iron itself can readily participate in redox reactions enabling vital processes, its reactivity also gives rise to reactive oxygen species (ROS). Hence, cancer cells further rely on antioxidant mechanisms to withstand such stress. The present review provides an overview of the common alterations of iron metabolism occurring in cancer and the mechanisms through which iron promotes tumor growth.

show abstract

Section: Systemic Iron Alterations In Cancermentioning

confidence: 97%

Iron: An Essential Element of Cancer Metabolism

Hsu

Mina

Roetto

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Furthermore, recent studies have revealed that hepcidin can be produced by cancer cells. For example, hepcidin expression was observed in normal breast cells and was significantly increased in breast cancer cells ( 25 , 48 ). Suppression of hepcidin synthesis by heparin, a potent inhibitor of liver-derived hepcidin production, induced significant inhibition of tumor growth due to diminished intracellular iron retention ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this notion, previous studies have demonstrated that hepcidin expression is upregulated in several types of cancer, including breast cancer, renal cell carcinoma (RCC), pancreatic cancer, prostate cancer, and colorectal cancer ( 23 ). In breast cancer patients, hepcidin expression in both serum and cancer tissues is significantly upregulated compared with that in normal individuals ( 24 , 25 ). Hepcidin exhibits diagnostic value in both breast cancer and breast cancer with bone metastasis ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Hepcidin Upregulation in Lung Cancer: A Potential Therapeutic Target Associated With Immune Infiltration

et al. 2021

View full text Add to dashboard Cite

Lung cancer has the highest death rate among cancers globally. Hepcidin is a fascinating regulator of iron metabolism; however, the prognostic value of hepcidin and its correlation with immune cell infiltration in lung cancer remain unclear. Here, we comprehensively clarified the prognostic value and potential function of hepcidin in lung cancer. Hepcidin expression was significantly increased in lung cancer. High hepcidin expression was associated with sex, age, metastasis, and pathological stage and significantly predicted an unfavorable prognosis in lung cancer patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results suggested that hepcidin is involved in the immune response. Furthermore, hepcidin expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, hepcidin may affect prognosis partially by regulating immune infiltration in lung cancer patients. Hepcidin may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in lung cancer.

show abstract

“…63 Taking this step further, a recent study explored that BMP6 is very important mediators for Hp synthesis in BC cell derived from MCF-7 and MCF-10a cell lines studied in 2D and 3D cell culture system. 4 Similar with prostate cancer and ovarian cancer, Fpn expression is reduced in breast cancer along with increased levels of the labile iron pool, TfR1, TfR2 and STEAP3. 24,34,67 In contrast, Hp (a negative regulator of FPN) was found to be increased in the patients present with BC as compared with health control.…”

Section: Dovepressmentioning

confidence: 96%

“…1 Approximately 12.5% of women in the United States have been affected by invasive breast cancer during their lifetime. [2][3][4] It is also the second most common prevalent cancerous disease among women living in sub-Saharan Africa (SSA) with increasing over time 1,5,6 and the survival rate of affected people are poor in this region. 7 The incidence rates differ considerably across African countries; for example, 64.2 new cases and 18.8 mortality per 100 000 women per year in Mauritius compared with 41.8 cases and 23 mortality rate per 100 000 women per year in Ethiopia.…”

Section: Introductionmentioning

confidence: 99%

<p>Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer</p>

Shibabaw

Teferi

Molla

et al. 2020

BCTT

View full text Add to dashboard Cite

Experimental and clinical data strongly support that iron is an essential element which plays a big role in cancer biology. Thus, hepcidin (Hp) and ferroportin (Fpn) are molecules that regulate and maintain the metabolism of iron. A peptide hormone hepcidin limits recycled and stored iron fluxes in macrophage and hepatic hepatocyte, respectively, to the blood stream by promoting degradation of the only iron exporter, Fpn, in the target cells. Moreover, the inflammatory microenvironment of breast cancer and altered hepcidin/ferroportin pathway is intimately linked. Breast cancer exhibits an iron seeking phenotype that is accomplished by tumor-associated macrophage (TAM). Because macrophages contribute to breast cancer growth and progression, this review will discuss TAM with an emphasis on describing how TAM (M2Ф phenotypic) interacts with their surrounding microenvironment and results in dysregulated Hp/Fpn and pathologic accumulation of iron as a hallmark of its malignant condition. Moreover, the underlying stroma or tumor microenvironment releases significant inflammatory cytokines like IL-6 and bone morphogenetic proteins like BMP-2 and 6 leading in aberrant Hp/Fpn pathways in breast cancer. Inflammation is primarily associated with the high intracellular iron levels, deregulated hepcidin/ferroportin pathway, and its upstream signaling in breast cancer. Subsequently, scholars have been reported that reducing iron level and manipulating the signaling molecules involved in iron metabolism can be used as a promising strategy of tumor chemotherapy. Here, we review the key molecular aspects of iron metabolism and its regulatory mechanisms of the hepcidin/ferroportin pathways and its current therapeutic strategies in breast cancer.

show abstract

New highlight in breast cancer development: the key role of hepcidin and iron metabolism

Cited by 10 publications

References 21 publications

Iron: An Essential Element of Cancer Metabolism

Iron: An Essential Element of Cancer Metabolism

Hepcidin Upregulation in Lung Cancer: A Potential Therapeutic Target Associated With Immune Infiltration

<p>Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer</p>

Contact Info

Product

Resources

About