Tucker Steven J, Zorn Alina J
School of Medicine, Medical Science and Nutrition, University of Aberdeen, Aberdeen, UK.
Br J Pharmacol. 2022 Jun;179(12):2829-2843. doi: 10.1111/bph.15403. Epub 2021 Feb 27.
The Popeye domain-containing protein 1 (POPDC1), a tight junction-associated transmembrane protein with a unique binding site for cAMP, has been shown to act as a tumour suppressor in cancer cells. Through interaction with many downstream effectors and signalling pathways, POPDC1 promotes cell adhesion and inhibits uncontrolled cell proliferation, epithelial-to-mesenchymal transition and metastasis. However, POPDC1 expression is down-regulated in many types of cancer, thereby reducing its tumour-suppressive actions. This review discusses the role of POPDC1 in the progression of the malignant phenotype and highlights the broad range of benefits POPDC1 stabilisation may achieve therapeutically. Cancer stem cells (CSCs) are a key hallmark of malignancies and commonly promote treatment resistance. This article provides a comprehensive overview of CSC signalling mechanisms, many of which have been shown to be regulated by POPDC1 in other cell types, thus suggesting an additional therapeutic benefit for POPDC1-stabilising anti-cancer drugs. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc.
含大力水手结构域蛋白1（POPDC1）是一种与紧密连接相关的跨膜蛋白，具有独特的环磷酸腺苷（cAMP）结合位点，已被证明在癌细胞中起肿瘤抑制作用。通过与许多下游效应器和信号通路相互作用，POPDC1促进细胞黏附并抑制细胞的失控增殖、上皮-间质转化和转移。然而，POPDC1在多种癌症类型中表达下调，从而降低了其肿瘤抑制作用。本综述讨论了POPDC1在恶性表型进展中的作用，并强调了稳定POPDC1在治疗上可能带来的广泛益处。癌症干细胞（CSCs）是恶性肿瘤的一个关键特征，通常会导致治疗耐药性。本文全面概述了癌症干细胞的信号传导机制，其中许多机制已被证明在其他细胞类型中受POPDC1调控，因此提示稳定POPDC1的抗癌药物可能具有额外的治疗益处。相关文章：本文是关于癌症预防与治疗新途径（《英国药理学杂志》75周年）主题系列的一部分。若要查看本专题的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc。
