HSPD1 promotes neuroblastoma by augmenting MYCN expression

Alassam, S. S.; Manikandan, D. B.; Ben-David, H.; Cohen, L.; Kaluski-Kopatch, S.; Hruby, L.; Dror, S.; Sorensen, P. H.; Delaidelli, A.; Leprivier, G.; Elkabets, M.; Rotblat, B. · cancer biology · 2026-09-06 · 原文

DOI：10.64898/2026.09.03.749066作者：12 位

MYCN amplification is associated with poor outcomes in neuroblastoma (NB). MYCN encodes a transcription factor that induces the expression of mitochondrial one-carbon enzymes and chaperones, promoting metabolic reprogramming and aggressiveness in NB tumor cells. While the contribution of MYCN to changes in the mitochondrial proteome is well established, how mitochondrial proteostasis contributes to MYCN activity remains poorly understood. Mitochondrial HSP60 (HSPD1) is a conserved mitochondrial chaperone promoting the mitochondrial one-carbon pathway and mitochondrial translation by folding the one-carbon enzyme MTHFD2 and preventing aggregation of mitochondrial ribosomal proteins. Here, we show that HSPD1 depletion in MYCN-amplified NB cells led to reduced mitochondrial translation, MYCN expression, and tumorigenesis in vitro and in vivo. In addition, HSPD1 mRNA and protein correlate with MYCN expression in NB tumors. These results establish HSPD1 as a promising target for the treatment of MYCN-amplified NB.

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1. 人话版

MYCN amplification is associated with poor outcomes in neuroblastoma (NB).

MYCN encodes a transcription factor that induces the expression of mitochondrial one-carbon enzymes and chaperones, promoting metabolic reprogramming and aggressiveness in NB tumor cells.

2. 领域脉络

本文类目：cancer biology，属于其所在研究脉络的最新进展。

3. 机制拆解

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4. 证据与数字

Mitochondrial HSP60 (HSPD1) is a conserved mitochondrial chaperone promoting the mitochondrial one-carbon pathway and mitochondrial translation by folding the one-carbon enzyme MTHFD2 and preventing aggregation of mitochondrial ribosomal proteins.

Here, we show that HSPD1 depletion in MYCN-amplified NB cells led to reduced mitochondrial translation, MYCN expression, and tumorigenesis in vitro and in vivo.

In addition, HSPD1 mRNA and protein correlate with MYCN expression in NB tumors.

5. 反例与边界

While the contribution of MYCN to changes in the mitochondrial proteome is well established, how mitochondrial proteostasis contributes to MYCN activity remains poorly understood.

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