Leibovitch Matthew, Topisirovic Ivan
Lady Davis Institute, SMBD JGH, McGill University, Montréal, QC, H3T 1E2, Canada.
Gerald Bronfman Department of Oncology, Montréal, QC, H3A 1A3, Canada; Department of Biochemistry, Montréal, QC, H3A 1A3, Canada; Department of Experimental Medicine McGill University, Montréal, QC, H3A 1A3, Canada; Lady Davis Institute, SMBD JGH, McGill University, Montréal, QC, H3T 1E2, Canada.
Adv Biol Regul. 2018 Jan;67:30-39. doi: 10.1016/j.jbior.2017.11.001. Epub 2017 Nov 2.
Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling underpins the vast majority of cancers whereby increased mTOR activity is thought to be a major determinant of both malignant translatomes and metabolomes. Nonetheless, the role of mTOR and other related signaling nodes (e.g. AMPK) in orchestrating protein synthesis and cancer energetics is only recently being unraveled. In this review, we discuss recent findings that provide insights into the molecular underpinnings of coordination of translational and metabolic programs of cancer cells, and potential strategies to translate these findings into clinical treatments.
mRNA翻译失调和能量代谢异常在癌症中很常见。鉴于mRNA翻译是一个耗能过程，癌细胞必须产生足够的ATP以满足过度活跃的翻译机制的能量需求。近年来，哺乳动物/雷帕霉素机制性靶标（mTOR）成为一个核心调节节点，它协调翻译装置的能量消耗和线粒体中的ATP生成。异常的mTOR信号传导是绝大多数癌症的基础，其中mTOR活性增加被认为是恶性翻译组和代谢组的主要决定因素。尽管如此，mTOR和其他相关信号节点（如AMPK）在协调蛋白质合成和癌症能量代谢方面的作用直到最近才被揭示。在这篇综述中，我们讨论了最近的研究发现，这些发现为癌细胞翻译和代谢程序协调的分子基础提供了见解，以及将这些发现转化为临床治疗的潜在策略。
