MYC 通过多种机制促进肿瘤生长。在这里，我们发现，在人类胶质母细胞瘤中，变体 MYC 转录物编码来自上游开放阅读框 (uORF) MPEP 的 114 个氨基酸肽，即 MYC 前 mRNA 编码蛋白 (MPEP)。分泌的 MPEP 通过直接结合和原肌球蛋白受体激酶 B (TRKB) 的激活（诱导下游 AKT-mTOR 信号传导）独立于 MYC，促进患者体内异种移植肿瘤的生长。通过基因消融靶向 MPEP 可减少患者来源的 4121 和 3691 胶质母细胞瘤干细胞的生长。 MPEP 中和抗体与小分子 TRKB 抑制剂联合使用可减少患者来源的异种移植肿瘤小鼠中胶质母细胞瘤的生长。 MPEP 在手术胶质母细胞瘤标本中的过度表达预示着预后不良，支持其临床相关性。总之，我们的结果表明，MYC 相关 uORF 的肿瘤特异性翻译促进胶质母细胞瘤生长，提出了胶质母细胞瘤的新治疗策略。

MYC promotes tumor growth through multiple mechanisms. Here, we show that, in human glioblastomas, the variant MYC transcript encodes a 114-amino acid peptide, MYC pre-mRNA encoded protein (MPEP), from the upstream open reading frame (uORF) MPEP. Secreted MPEP promotes patient-derived xenograft tumor growth in vivo, independent of MYC through direct binding, and activation of tropomyosin receptor kinase B (TRKB), which induces downstream AKT-mTOR signaling. Targeting MPEP through genetic ablation reduced growth of patient-derived 4121 and 3691 glioblastoma stem cells. Administration of an MPEP-neutralizing antibody in combination with a small-molecule TRKB inhibitor reduced glioblastoma growth in patient-derived xenograft tumor-bearing mice. The overexpression of MPEP in surgical glioblastoma specimens predicted a poor prognosis, supporting its clinical relevance. In summary, our results demonstrate that tumor-specific translation of a MYC-associated uORF promotes glioblastoma growth, suggesting a new therapeutic strategy for glioblastoma.