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

Abstract

A B S T R A C TMany 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.

Loss of Proprotein Convertase Furin in Mammary Gland Impairs proIGF1R and proIR Processing and Suppresses Tumorigenesis in Triple Negative Breast Cancer

“…Furin, together with six other members (PC1/3, PC2, PC4, PACE4, PC5/6 and PC7), constitute the proprotein convertase (PC) family that is responsible for the cleavage and activation of various protein precursors in cells [3]. Maturation of several of these precursors is required for various processes including tumor initiation, progression and metastasis [4]. Previously, Cheng et al reported that mRNA expression of Furin in human breast cancer was much higher compared to adjacent breast tissues [5], suggesting that Furin might play an important role in breast cancer.…”

Furin Prodomain Ppfurin Enhances Soce Through trpc6 Activation in Breast Cancer Cells

“…In many circumstances, changes in [Ca 2+ ]i are controlled by intracellular Ca 2+ store mobilization and Ca 2+ influx through hormones, growth factor receptors activation [2][3][4]. Interestingly, wide range of these secretory proteins are synthesized as inactive precursors that are converted to their bioactive forms at the general motif (K/R)-(X)n-(K/R), where n= 0, 2, 4 or 6 by Furin-like enzymes [5][6][7][8].…”

“…Furin, also known as PCSK3, is a proprotein convertase that belongs to a family of Ca 2+ -dependent serine peptidases. Synthesized as a precursor protein (preppFurin), this enzyme requires autocleavage in the secretory pathway for its activation [5,9,10]. Following the removal of the "pre" signal peptide in the endoplasmic reticulum (ER), the remaining protein is than autocatalytically processed in the secretory pathway to generate the N-terminal ppFurin fragment and mature active Furin.…”

Union is strength: antiviral and anti-inflammatory drugs for COVID-19

“…This is in agreement with observations on the importance of the positive charge of furin inhibitors [58] . Notably, recent evidence showed that furin and other proprotein convertases have a role in inflammatory malignancies [59] . Therefore, targeting furin could be a way to contain viral infection and inflammation.…”