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Review
. 2020 Mar 31:473:50-61.
doi: 10.1016/j.canlet.2019.12.027. Epub 2019 Dec 30.

Proprotein convertases: Key players in inflammation-related malignancies and metastasis

Geraldine Siegfried  1 , Jean Descarpentrie  2 , Serge Evrard  3 , Abdel-Majid Khatib  4
Affiliations
Review

Proprotein convertases: Key players in inflammation-related malignancies and metastasis

Geraldine Siegfried et al. Cancer Lett. .

Abstract

Many cancers occur from locations of inflammation due to chronic irritation and/or infection. Tumor microenvironment contains various different inflammatory cells and mediators that orchestrate diverse neoplastic processes, including proliferation, survival, adhesion and migration. In parallel, tumor cells have adapted some of the signaling molecules used by inflammatory cells, such as selectins and chemokines as well as their receptors for invasion, extravasation and subsequently metastasis. Expression and/or activation of the majority of these molecules is mediated by the proprotein convertases (PCs); proteases expressed by both tumor cells and inflammatory cells. This review analyzes the potential role of these enzymatic system in inflammation-associated cancer impacting on the malignant and metastatic potential of cancer cells, describing the possible use of PCs as a new anti-inflammatory therapeutic approach to tumor progression and metastasis.

Keywords: Metastasis; Protein maturation; Substrates; α1-PDX.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic representation of inflammation-related pathways leading to cancer and metastasis.
Fig. 2
Fig. 2
Schematic representation of the primary structure of the proprotein convertases (PCs). The primary structures and domains of the nine PCs including the two alternative spliced forms of PC5/6 PC5/6A and PC5/6B are shown. The signal peptide, the prosegment, and the catalytic domain with typical catalytic triad residues Asp, His, and Ser are common to all the PCs. The other domains and the number of the amino acid (aa) for each proprotein convertase (PC) are also indicated.
Fig. 3
Fig. 3
Biological functions involving the proprotein convertases (PCs) leading to cancer.
Fig. 4
Fig. 4
Schematic representation of inflammatory mediators and proprotein convertases (PCs) cross-talk. Substrates and downstream effectors of the PCs (I) leading to inflammation (II). The latter mediates various biological processes (III) responsible for tumor progression and metastasis (IV). The ability of some PC substrates to induce several PCs expression is also indicated.
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