Département de Biochimie et Médicine Moléculaire, Université de Montréal, Succursale Centre-Ville, Montréal, QC, C.P. 6128, Canada.
Hôpital Maisonneuve-Rosemont Research Centre, 5415 Assumption Blvd, Montréal, QC, H1T 2M4, Canada.
Cell Oncol (Dordr). 2022 Oct;45(5):831-859. doi: 10.1007/s13402-022-00706-4. Epub 2022 Aug 29.
Prostate cancer is the leading cause of cancer in men, and its incidence increases with age. Among other risk factors, pre-existing metabolic diseases have been recently linked with prostate cancer, and our current knowledge recognizes prostate cancer as a condition with important metabolic anomalies as well. In malignancies, metabolic disorders are commonly associated with aberrations in mTOR, which is the master regulator of protein synthesis and energetic homeostasis. Although there are reports demonstrating the high dependency of prostate cancer cells for lipid derivatives and even for carbohydrates, the understanding regarding amino acids, and the relationship with the mTOR pathway ultimately resulting in metabolic aberrations, is still scarce.
In this review, we briefly provide evidence supporting prostate cancer as a metabolic disease, and discuss what is known about mTOR signaling and prostate cancer. Next, we emphasized on the amino acids glutamine, leucine, serine, glycine, sarcosine, proline and arginine, commonly related to prostate cancer, to explore the alterations in their regulatory pathways and to link them with the associated metabolic reprogramming events seen in prostate cancer. Finally, we display potential therapeutic strategies for targeting mTOR and the referred amino acids, as experimental approaches to selectively attack prostate cancer cells.
前列腺癌是男性癌症的主要病因，其发病率随着年龄的增长而增加。在其他风险因素中，先前存在的代谢疾病最近与前列腺癌有关，我们目前的知识也将前列腺癌视为一种存在重要代谢异常的疾病。在恶性肿瘤中，代谢紊乱通常与 mTOR 的异常有关，mTOR 是蛋白质合成和能量平衡的主调控因子。尽管有报道表明前列腺癌细胞对脂质衍生物甚至碳水化合物有很高的依赖性，但关于氨基酸以及与 mTOR 途径的关系最终导致代谢异常的理解仍然很少。
在这篇综述中，我们简要提供了支持前列腺癌作为一种代谢疾病的证据，并讨论了已知的 mTOR 信号和前列腺癌。接下来，我们强调了与前列腺癌相关的常见氨基酸谷氨酰胺、亮氨酸、丝氨酸、甘氨酸、肌氨酸、脯氨酸和精氨酸，探讨了它们调节途径的改变，并将其与前列腺癌中观察到的相关代谢重编程事件联系起来。最后，我们展示了针对 mTOR 和所述氨基酸的潜在治疗策略，作为选择性攻击前列腺癌细胞的实验方法。
