Guo Peng, Wu Chenchun, Wang Tong, Song Yajuan, Liu Xiaozi, Wang Xiang, Zhu Yuhan, Song Binyu, Zhu Yifu, Zhang Juan, Guo Lei, Tao Rui, Yu Zhou, Song Baoqiang
Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Burn and Plastic Surgery, The 990th Hospital of the Joint Logistic Support Force, Zhumadian, China.
J Enzyme Inhib Med Chem. 2025 Dec;40(1):2545620. doi: 10.1080/14756366.2025.2545620. Epub 2025 Sep 2.
Pyrroline-5-Carboxylate Reductase 1 (PYCR1), a member of the PYCR family, is a key enzyme in the proline biosynthesis pathway. Notably, PYCR1 was originally identified via genetic disease research, linking its mutations to the occurrence of cutis laxa. PYCR1 contributes to the pathogenesis of malignancies and fibrotic diseases via mechanisms involving metabolic reprogramming, Extracellular Matrix (ECM) remodelling, and redox homeostasis maintenance. PYCR1 upregulation has been reported in multiple malignancies including Hepatocellular Carcinoma (HCC), Lung Cancer (LC), Breast Cancer (BC), Bladder Cancer (BlC), and Gastric Cancer (GC), where it has been shown to promote cancer proliferation, migration, and therapy resistance, correlating significantly with advanced cancer stages and poor prognosis. On the other hand, in fibrotic disorders, PYCR1-mediated proline metabolism has been linked to the progression of pulmonary, myocardial, and cutaneous fibroses. Notably, although PYCR1-targeted small-molecule inhibitors have demonstrated therapeutic potential in preclinical studies, their clinical translation is yet to be validated.
吡咯啉-5-羧酸还原酶1（PYCR1）是PYCR家族的成员之一，是脯氨酸生物合成途径中的关键酶。值得注意的是，PYCR1最初是通过遗传疾病研究确定的，其突变与皮肤松弛症的发生有关。PYCR1通过涉及代谢重编程、细胞外基质（ECM）重塑和氧化还原稳态维持的机制，促进恶性肿瘤和纤维化疾病的发病机制。在包括肝细胞癌（HCC）、肺癌（LC）、乳腺癌（BC）、膀胱癌（BlC）和胃癌（GC）在内的多种恶性肿瘤中，均有PYCR1上调的报道，在这些肿瘤中，PYCR1已被证明可促进癌症增殖、迁移和治疗耐药性，与癌症晚期和不良预后显著相关。另一方面，在纤维化疾病中，PYCR1介导的脯氨酸代谢与肺、心肌和皮肤纤维化的进展有关。值得注意的是，尽管针对PYCR1的小分子抑制剂在临床前研究中已显示出治疗潜力，但其临床转化尚未得到验证。
