The metabolism of the non-essential amino acid L-proline is emerging as a key pathway in the metabolic rewiring that sustains cancer cells proliferation, survival and metastatic spread. Pyrroline-5-carboxylate reductase (PYCR) and proline dehydrogenase (PRODH) enzymes, which catalyze the last step in proline biosynthesis and the first step of its catabolism, respectively, have been extensively associated with the progression of several malignancies, and have been exposed as potential targets for anticancer drug development. As investigations into the links between proline metabolism and cancer accumulate, the complexity, and sometimes contradictory nature of this interaction emerge. It is clear that the role of proline metabolism enzymes in cancer depends on tumor type, with different cancers and cancer-related phenotypes displaying different dependencies on these enzymes. Unexpectedly, the outcome of rewiring proline metabolism also differs between conditions of nutrient and oxygen limitation. Here, we provide a comprehensive review of proline metabolism in cancer; we collate the experimental evidence that links proline metabolism with the different aspects of cancer progression and critically discuss the potential mechanisms involved.

非必需氨基酸L-脯氨酸的代谢正在成为代谢重排中的关键途径，这种代谢重排可维持癌细胞的增殖，存活和转移扩散。分别催化脯氨酸生物合成的最后一步和其分解代谢的第一步的吡咯烷-5-羧酸还原酶（PYCR）和脯氨酸脱氢酶（PRODH）酶已与多种恶性肿瘤的发展密切相关，并且已经暴露出来作为抗癌药物开发的潜在目标。随着对脯氨酸代谢和癌症之间联系的研究的积累，这种相互作用的复杂性，有时甚至是矛盾的性质出现了。很明显，脯氨酸代谢酶在癌症中的作用取决于肿瘤类型，具有不同的癌症和与癌症相关的表型，对这些酶表现出不同的依赖性。出乎意料的是，在营养和氧气限制条件之间，脯氨酸代谢重新连接的结果也有所不同。在这里，我们提供了癌症中脯氨酸代谢的全面综述；我们整理了将脯氨酸代谢与癌症进展的不同方面联系起来的实验证据，并严格讨论了其中涉及的潜在机制。