Open Access

Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma

  • Authors:
    • Fengping Yao
    • Xiaohong Cui
    • Ying Zhang
    • Zhuchun Bei
    • Hongquan Wang
    • Dongxu Zhao
    • Hong Wang
    • Yongfei Yang
  • View Affiliations

  • Published online on: July 12, 2021     https://doi.org/10.3892/ol.2021.12918
  • Article Number: 657
  • Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melanoma, the most aggressive skin cancer, is mainly treated with BRAF inhibitors or immunotheareapy. However, most patients who initially responded to BRAF inhibitors or immunotheareapy become resistant following relapse. Ferroptosis is a form of regulated cell death characterized by its dependence on iron ions and the accumulation of lipid reactive oxygen species (ROS). Recent studies have demonstrated that ferroptosis is a good method for tumor treatment, and iron homeostasis is closely associated with ferroptosis. Iron regulatory protein (IRP)1 and 2 play important roles in maintaining iron homeostasis, but their functions in ferroptosis have not been investigated. The present study reported that the expression of IRP1 and IRP2 was increased by the ferroptosis inducers erastin and RSL3 in melanoma cells. Depletion of IRP1 significantly suppressed erastin‑ and RSL3‑induced ferroptosis. IRP2 had a weak effect but could enhance the promoting function of IRP1 on ferroptosis. Further, erastin and RSL3 promoted the transition of aconitase 1 to IRP1, which regulated downstream iron metabolism proteins, including transferrin receptor (TFRC), ferroportin (FPN) and ferritin heavy chain 1 (FTH1). Moreover, overexpression of TFRC and knockdown of FPN and FTH1 significantly promoted erastin‑ and RSL3‑induced ferroptosis in IRP1 knockdown melanoma cells. Collectively, the present findings indicate that IRP1 plays an essential role in erastin‑ and RSL3‑induced ferroptosis by regulating iron homeostasis.
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September-2021
Volume 22 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yao F, Cui X, Zhang Y, Bei Z, Wang H, Zhao D, Wang H and Yang Y: Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma. Oncol Lett 22: 657, 2021
APA
Yao, F., Cui, X., Zhang, Y., Bei, Z., Wang, H., Zhao, D. ... Yang, Y. (2021). Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma. Oncology Letters, 22, 657. https://doi.org/10.3892/ol.2021.12918
MLA
Yao, F., Cui, X., Zhang, Y., Bei, Z., Wang, H., Zhao, D., Wang, H., Yang, Y."Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma". Oncology Letters 22.3 (2021): 657.
Chicago
Yao, F., Cui, X., Zhang, Y., Bei, Z., Wang, H., Zhao, D., Wang, H., Yang, Y."Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma". Oncology Letters 22, no. 3 (2021): 657. https://doi.org/10.3892/ol.2021.12918