[[Transferrin receptor]] [[protein]] 1 (TfR1), also known as Cluster of Differentiation 71 ([[CD71]]), is a protein that in humans is encoded by the TFRC gene.

TfR1 is required for iron import from transferrin into cells by [[endocytosis]].
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[[MYCN]] amplification is tightly associated with the poor prognosis of pediatric [[neuroblastoma]] (NB). The regulation of NB [[cell death]] by MYCN represents an important aspect, as it directly contributes to [[tumor progression]] and therapeutic resistance. However, the relationship between MYCN and cell death remains elusive. [[Ferroptosis]] is a newly identified cell death mode featured by [[lipid peroxide]] accumulation that can be attenuated by [[GPX4]], yet whether and how MYCN regulates ferroptosis are not fully understood. 

Lu et al. reported MYCN-amplified NB cells are sensitive to GPX4-targeting ferroptosis inducers. Mechanically, MYCN expression reprograms the cellular [[iron metabolism]] by upregulating the expression of [[TFRC]], which encodes [[transferrin receptor 1]] as a key iron transporter on the cell membrane. Further, the increased [[iron]] uptake promotes the accumulation of labile iron pool, leading to enhanced [[lipid peroxide]] production. Consistently, TFRC overexpression in NB cells also induces selective sensitivity to GPX4 inhibition and ferroptosis. Moreover, they found that MYCN fails to alter the general [[lipid metabolism]] and the amount of [[cystine]] imported by System Xc(-) for [[glutathione]] synthesis, both of which contribute to ferroptosis in alternative contexts. In conclusion, NB cells harboring [[MYCN]] amplification are prone to undergo [[ferroptosis]] conferred by [[TFRC]] upregulation, suggesting that [[GPX4]]-targeting ferroptosis inducers or [[TFRC]] agonists can be potential strategies in treating MYCN-amplified NB
((Lu Y, Yang Q, Su Y, Ji Y, Li G, Yang X, Xu L, Lu Z, Dong J, Wu Y, Bei JX, Pan C, Gu X, Li B. MYCN mediates TFRC-dependent ferroptosis and reveals vulnerabilities in neuroblastoma. Cell Death Dis. 2021 May 19;12(6):511. doi: 10.1038/s41419-021-03790-w. PMID: 34011924.)).