Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

Jeong, Seung Min; Hwang, Sun-Mi; Seong, Rho Hyun

doi:10.1016/j.bbrc.2016.02.023

Cited by 94 publications

(76 citation statements)

References 29 publications

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“…KRAS can upregulate ROS through multiple mechanisms. For example, KRAS can regulate HIF‐1α and HIF‐2α target genes to modulate mitochondrial metabolism or regulate the transferrin receptor (TFRC) to modulate mitochondrial respiration and ROS generation . Notably, TFRC is a regulator in ferroptosis, as mentioned above.…”

Section: Role Of Kras In Ferroptosismentioning

confidence: 99%

Ferroptosis: Final destination for cancer?

et al. 2020

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Ferroptosis is a recently defined, non‐apoptotic, regulated cell death (RCD) process that comprises abnormal metabolism of cellular lipid oxides catalysed by iron ions or iron‐containing enzymes. In this process, a variety of inducers destroy the cell redox balance and produce a large number of lipid peroxidation products, eventually triggering cell death. However, in terms of morphology, biochemistry and genetics, ferroptosis is quite different from apoptosis, necrosis, autophagy‐dependent cell death and other RCD processes. A growing number of studies suggest that the relationship between ferroptosis and cancer is extremely complicated and that ferroptosis promises to be a novel approach for the cancer treatment. This article primarily focuses on the mechanism of ferroptosis and discusses the potential application of ferroptosis in cancer therapy.

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Section: Role Of Kras In Ferroptosismentioning

confidence: 99%

Ferroptosis: Final destination for cancer?

et al. 2020

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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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“…In another study it was shown that reduced superoxide levels mediated by ectopic expression of SOD isoenzymes (extracellular, manganese, and copper-zinc) inhibited the growth of MiaPaca2 pancreatic cancer cells and diminished their ability to form tumors in vivo [72]. In addition, pancreatic cancer cell growth is also promoted by the transferrin receptor (TfR1) in a manner which is dependent on the receptors’ ability to support mitochondrial respiration and the accompanying ROS production [73]. …”

Section: Ros In Pda Progressionmentioning

confidence: 99%

Targeting reactive oxygen species in development and progression of pancreatic cancer

Durand

Störz

2016

Expert Review of Anticancer Therapy

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Introduction Pancreatic ductal adenocarcinoma (PDA) is characterized by expression of oncogenic KRas which drives all aspects of tumorigenesis. Oncogenic KRas induces the formation of reactive oxygen species (ROS) which have been implicated in initiation and progression of PDA. To facilitate tumor promoting levels and to avoid oncogene-induced senescence or cytotoxicity, ROS homeostasis in PDA cells is balanced by additional up-regulation of antioxidant systems. Areas Covered We examine the sources of ROS in PDA, the mechanisms by which ROS homeostasis is maintained, and the biological consequences of ROS in PDA. Additionally, we discuss the potential mechanisms for targeting ROS homoeostasis as a point of therapeutic intervention. An extensive review of the relevant literature as it relates to the topic was conducted using PubMed. Expert Commentary Even though oncogenic mutations in the KRAS gene have been detected in over 95% of human pancreatic adenocarcinoma, targeting its gene product, KRas, has been difficult. The dependency of PDA cells on balancing ROS homeostasis could be an angle for new prevention or treatment strategies. These include use of antioxidants to prevent formation or progression of precancerous lesions, or methods to increase ROS in tumor cells to toxic levels.

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Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

Cited by 94 publications

References 29 publications

Ferroptosis: Final destination for cancer?

Ferroptosis: Final destination for cancer?

Targeting iron metabolism in drug discovery and delivery

Targeting reactive oxygen species in development and progression of pancreatic cancer

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