Human STEAP3 maintains tumor growth under hypoferric condition

Isobe, Taichi; Baba, Eishi; Arita, Shuji; Komoda, Masato; Tamura, Shingo; Shirakawa, Tsuyoshi; Ariyama, Hiroshi; Takaishi, Shigeo; Kusaba, Hitoshi; Ueki, Takashi; Akashi, Koichi

doi:10.1016/j.yexcr.2011.07.022

Cited by 38 publications

(35 citation statements)

References 32 publications

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“…In mouse models, STEAP3 overexpression in Raji cells, a line derived from Burkitt lymphoma, allowed the tumor growth to persist when low iron levels would normally encourage apoptosis [24]. Therefore, this gene may be responsible for a resilience to hypoferric conditions in multiple cancers, leading to a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

Aberrations in the Iron Regulatory Gene Signature Are Associated with Decreased Survival in Diffuse Infiltrating Gliomas

et al. 2016

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Iron is a tightly regulated micronutrient with no physiologic means of elimination and is necessary for cell division in normal tissue. Recent evidence suggests that dysregulation of iron regulatory proteins may play a role in cancer pathophysiology. We use public data from The Cancer Genome Atlas (TCGA) to study the association between survival and expression levels of 61 genes coding for iron regulatory proteins in patients with World Health Organization Grade II-III gliomas. Using a feature selection algorithm we identified a novel, optimized subset of eight iron regulatory genes (STEAP3, HFE, TMPRSS6, SFXN1, TFRC, UROS, SLC11A2, and STEAP4) whose differential expression defines two phenotypic groups with median survival differences of 52.3 months for patients with grade II gliomas (25.9 vs. 78.2 months, p< 10−3), 43.5 months for patients with grade III gliomas (43.9 vs. 87.4 months, p = 0.025), and 54.0 months when considering both grade II and III gliomas (79.9 vs. 25.9 months, p < 10−5).

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Section: Discussionmentioning

confidence: 99%

Aberrations in the Iron Regulatory Gene Signature Are Associated with Decreased Survival in Diffuse Infiltrating Gliomas

et al. 2016

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“…There is, however, clear evidence that deregulated iron homeostasis on a local — that is, microenvironmental and/or cellular — level is associated with tumour progression, as illustrated by changes in expression of iron-related genes in cancer cells (Figure 4), the levels of which are inversely correlated with patient survival90–92. In the context of tumour progression, one can envision that proliferating cancer cells, which require substantial amounts of iron to support their growth, will attempt to increase their iron intake, for example by increasing the expression of TfR193–95 and STEAP396,97; to modulate iron storage capacity by producing ferritin94,96; and to limit their iron export by downregulating ferroportin91,98–100. However, the additional intracellular oxidative stress that is accompanied by the increased presence of labile iron may also make them more sensitive to ferroptosis65,67 and hinder tumour metastasis85, illustrating the complex relationship between iron, ROS and cancer cell survival.…”

Section: Iron and The Pathophysiology Of Diseasementioning

confidence: 99%

Targeting iron metabolism in drug discovery and delivery

Crielaard

Lammers

Rivella

2017

Nat Rev Drug Discov

290

205

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Iron fulfils a central role in many essential biochemical processes in human physiology, which makes proper processing of iron crucial. Although iron metabolism is subject to relatively strict physiological control, in recent years numerous disorders, such as cancer and neurodegenerative diseases, have been linked to deregulated iron homeostasis. Because of its involvement in the pathogenesis of these diseases, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents will likely have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are often available.

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“…Steap3 null mice display severe microcytic anemia due to reduced ferric reductase activity and abnormal erythroid maturation . Because iron is irreplaceable in the functions of ribonucleotide reductase and the mitochondrial respiratory chain, Steap3 may influence cellular fate toward proliferation or apoptosis by regulating the intracellular iron content . In addition, Steap3 can promote tumor cell apoptosis to inhibit tumor cell proliferation and metastasis through caspase‐3‐dependent pathways .…”

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confidence: 99%

“…(14) Because iron is irreplaceable in the functions of ribonucleotide reductase and the mitochondrial respiratory chain, Steap3 may influence cellular fate toward proliferation or apoptosis by regulating the intracellular iron content. (15) In addition, Steap3 can promote tumor cell apoptosis to inhibit tumor cell proliferation and metastasis through caspase-3-dependent pathways. (16) Moreover, Steap3 deficiency is reported to impair the toll-like receptor 4 (TLR4)-mediated inflammatory response.…”

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confidence: 99%

Six‐Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia‐Reperfusion Injury by Suppressing Transforming Growth Factor‐β‐Activated Kinase 1

et al. 2019

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Background and Aims Hepatic ischemia‐reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function after hepatic I/R injury are limited. Six‐transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types. However, the role of Steap3 in hepatic I/R‐induced liver damage remains largely unclear. Approach and Results In the present study, we found that Steap3 expression was significantly up‐regulated in liver tissue from mice subjected to hepatic I/R surgery and primary hepatocytes challenged with hypoxia/reoxygenation insult. Subsequently, global Steap3 knockout (Steap3‐KO) mice, hepatocyte‐specific Steap3 transgenic (Steap3‐HTG) mice, and their corresponding controls were subjected to partial hepatic warm I/R injury. Hepatic histology, the inflammatory response, and apoptosis were monitored to assess liver damage. The molecular mechanisms of Steap3 function were explored in vivo and in vitro. The results demonstrated that, compared with control mice, Steap3‐KO mice exhibited alleviated liver damage after hepatic I/R injury, as shown by smaller necrotic areas, lower serum transaminase levels, decreased apoptosis rates, and reduced inflammatory cell infiltration, whereas Steap3‐HTG mice had the opposite phenotype. Further molecular experiments showed that Steap3 deficiency could inhibit transforming growth factor‐β–activated kinase 1 (TAK1) activation and downstream c‐Jun N‐terminal kinase (JNK) and p38 signaling during hepatic I/R injury. Conclusions Steap3 is a mediator of hepatic I/R injury that functions by regulating inflammatory responses as well as apoptosis through TAK1‐dependent activation of the JNK/p38 pathways. Targeting hepatocytes, Steap3 may be a promising approach to protect the liver against I/R injury.

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Human STEAP3 maintains tumor growth under hypoferric condition

Cited by 38 publications

References 32 publications

Aberrations in the Iron Regulatory Gene Signature Are Associated with Decreased Survival in Diffuse Infiltrating Gliomas

Aberrations in the Iron Regulatory Gene Signature Are Associated with Decreased Survival in Diffuse Infiltrating Gliomas

Targeting iron metabolism in drug discovery and delivery

Six‐Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia‐Reperfusion Injury by Suppressing Transforming Growth Factor‐β‐Activated Kinase 1

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