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Prokineticin 1 (PROK1), also known as Endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), is a secreted protein that plays a critical role in tissue-specific angiogenesis, particularly within endocrine organs such as the ovaries, testes, and adrenal glands [1, 2]. It functions by binding to two G protein-coupled receptors, PROKR1 and PROKR2, triggering signaling pathways that promote cell proliferation, survival, and migration [1, 5]. In pathological contexts, PROK1 is frequently overexpressed in various cancers, including colorectal and pancreatic carcinomas, where it facilitates tumor vascularization and metastasis [3]. Additionally, dysregulation of PROK1 is strongly associated with reproductive disorders such as preeclampsia, endometriosis, and polycystic ovary syndrome (PCOS) [4]. Therapeutic strategies targeting PROK1 include the development of neutralizing antibodies, small molecule receptor antagonists like PKRA7, and RNA-based interventions like siRNA designed to degrade PROK1 mRNA [6, 8]. While promising for treating angiogenesis-dependent diseases, targeting this pathway requires careful consideration of its essential roles in normal reproductive and endocrine physiology [4].
Antagonism of prokineticin receptors (PROKR1/2) to block downstream signaling, or RNA interference (siRNA) to degrade PROK1 mRNA and prevent protein synthesis.
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