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The proprotein convertase furin in cancer: more than an oncogene

Oncogene volume 41, pages 1252–1262 (2022)Cite this article

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Abstract

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.

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Fig. 1: Schematic illustration of the structural template of the proprotein convertases.
Fig. 2: The expression level of Furin in the different blood cell types.
Fig. 3: Schematic representation of proproteins processing and/or activation by Furin.
Fig. 4: Predicted Furin substrates enriched signaling pathways.
Fig. 5: The expression level of Furin gene in human tumor samples and paired normal tissue.
Fig. 6: Landscape of genomic aberrations of Furin gene in cancer.

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Acknowledgements

We would like to thank Sandra McElroy for proofreading manuscript. We acknowledge grant support from FWO Vlaanderen (Grant no. G.0738.15) to JC.

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  1. These authors contributed equally: Abdel-Majid Khatib, John W. M. Creemers.

Authors and Affiliations

  1. Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China

    Zongsheng He

  2. Laboratory of Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven, Belgium

    Zongsheng He & John W. M. Creemers

  3. INSERM, LAMC, UMR 1029, Allée Geoffroy St Hilaire, Pessac, France

    Abdel-Majid Khatib

  4. Institut Bergoinié, Bordeaux, France

    Abdel-Majid Khatib

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ZH conceived and wrote the manuscript with the contribution of AMK and JC. AMK and JC critically revised the manuscript. The figures of the manuscript were conceived and designed by ZH with input from AMK and JC. All authors have read and approved the final version of the manuscript.

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He, Z., Khatib, AM. & Creemers, J.W.M. The proprotein convertase furin in cancer: more than an oncogene. Oncogene 41, 1252–1262 (2022). https://doi.org/10.1038/s41388-021-02175-9

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