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This study identifies HSPD1, a mitochondrial chaperone protein, as a key regulator of MYCN expression in neuroblastoma cells. Researchers found that depleting HSPD1 in MYCN-amplified neuroblastoma cells reduced mitochondrial translation, decreased MYCN protein levels, and suppressed tumor growth both in laboratory cultures and in animal models. The correlation between HSPD1 and MYCN expression levels in patient tumors suggests HSPD1 maintains MYCN activity through its role in mitochondrial protein folding and metabolic function.
Why it matters
MYCN-amplified neuroblastoma is associated with aggressive disease and poor patient outcomes, and MYCN itself has been difficult to target directly with drugs. This research identifies HSPD1 as a potentially druggable target that could indirectly reduce MYCN activity, offering a new therapeutic strategy for high-risk neuroblastoma patients.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
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.
Source: HSPD1 promotes neuroblastoma by augmenting MYCN expression