The proprotein convertase furin in cancer: more than an oncogene.

Zongsheng He, Abdel-Majid Khatib, John W M Creemers

Oncogene 2022 Feb

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Furin is the first discovered proprotein convertase member and is present in almost all mammalian cells. Therefore, by regulating the maturation of a wide range of proproteins, Furin expression and/or activity is involved in various physiological and pathophysiological processes ranging from embryonic development to carcinogenesis. Since many of these protein precursors are involved in initiating and maintaining the hallmarks of cancer, Furin has been proposed as a potential target for treating several human cancers. In contrast, other studies have revealed that some types of cancer do not benefit from Furin inhibition. Therefore, understanding the heterogeneous functions of Furin in cancer will provide important insights into the design of effective strategies targeting Furin in cancer treatment. Here, we present recent advances in understanding how Furin expression and activity are regulated in cancer cells and their influences on the activity of Furin substrates in carcinogenesis. Furthermore, we discuss how Furin represses tumorigenic properties of several cancer cells and why Furin inhibition leads to aggressive phenotypes in other tumors. Finally, we summarize the clinical applications of Furin inhibition in treating human cancers. © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Zongsheng He, Abdel-Majid Khatib, John W M Creemers. The proprotein convertase furin in cancer: more than an oncogene. Oncogene. 2022 Feb;41(9):1252-1262