====== MYCN ======

N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the [[MYCN]] gene.
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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.)).
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Glioblastoma with primitive neuronal components was added as a pattern in glioblastoma. This pattern previously referred to in the literature as glioblastoma with PNET-like component, is usually comprised of a diffuse astrocytoma of any grade (or oligodendroglioma in rare cases) that has well-demarcated nodules containing primitive cells that display neuronal differentiation (e.g., Homer Wright rosettes, a gain of synaptophysin positivity and loss of GFAP expression) and that sometimes has MYC or [[MYCN]] amplification; these tumors have a tendency for craniospinal fluid dissemination.
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Estiar MA, Javan F, Zekri A, Mehrazin M, Mehdipour P. Prognostic
significance of [[MYCN]] gene amplification and protein expression in primary brain
tumors: Astrocytoma and meningioma. Cancer Biomark. 2017 Jul 4;19(3):341-351.
doi: 10.3233/CBM-160546. PubMed PMID: 28453467.
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Sin-Chan P, Mumal I, Suwal T, Ho B, Fan X, Singh I, Du Y, Lu M, Patel N,
Torchia J, Popovski D, Fouladi M, Guilhamon P, Hansford JR, Leary S, Hoffman LM,
Mulcahy Levy JM, Lassaletta A, Solano-Paez P, Rivas E, Reddy A, Gillespie GY,
Gupta N, Van Meter TE, Nakamura H, Wong TT, Ra YS, Kim SK, Massimi L, Grundy RG,
Fangusaro J, Johnston D, Chan J, Lafay-Cousin L, Hwang EI, Wang Y, Catchpoole D,
Michaud J, Ellezam B, Ramanujachar R, Lindsay H, Taylor MD, Hawkins CE, Bouffet
E, Jabado N, Singh SK, Kleinman CL, Barsyte-Lovejoy D, Li XN, Dirks PB, Lin CY,
Mack SC, Rich JN, Huang A. A C19MC-LIN28A-[[MYCN]] Oncogenic Circuit Driven by
Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A
Lethal Brain Tumor. Cancer Cell. 2019 Jul 8;36(1):51-67.e7. doi:
10.1016/j.ccell.2019.06.002. PMID: 31287992.