From the Division of Endocrinology Mayo ClinicRochester, Minnesota, USA
Department of Molecular Biology and GeneticsAarhus University, Aarhus, Denmark.
J Mol Endocrinol. 2018 Jul;61(1):T1-T10. doi: 10.1530/JME-17-0236.
The zinc metalloproteinase, PAPP-A, enhances local insulin-like growth factor (IGF) action through cleavage of inhibitory IGF-binding proteins, thereby increasing IGF available for IGF receptor-mediated cell proliferation, migration and survival. In many tumors, enhanced IGF receptor signaling is associated with tumor growth, invasion and metastasis. We will first discuss PAPP-A structure and function, and post-translational inhibitors of PAPP-A expression or proteolytic activity. We will then review the evidence supporting an important role for PAPP-A in many cancers, including breast, ovarian and lung cancer, and Ewing sarcoma.
锌金属蛋白酶 PAPP-A 通过切割抑制性 IGF 结合蛋白来增强局部胰岛素样生长因子 (IGF) 作用，从而增加 IGF 受体介导的细胞增殖、迁移和存活的 IGF 供应。在许多肿瘤中，增强的 IGF 受体信号与肿瘤生长、侵袭和转移有关。我们将首先讨论 PAPP-A 的结构和功能，以及 PAPP-A 表达或蛋白水解活性的翻译后抑制剂。然后，我们将回顾支持 PAPP-A 在许多癌症（包括乳腺癌、卵巢癌和肺癌以及尤因肉瘤）中的重要作用的证据。
