The proprotein convertase furin in tumour progression

Jaaks, Patricia; Bernasconi, Michele

doi:10.1002/ijc.30714

Cited by 115 publications

(122 citation statements)

References 124 publications

(226 reference statements)

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“…Although it is also known that furin promotes many cancer-related processes including cell proliferation, migration and invasion [2,27], we did not find an association with total cancer incidence. However, we report in the present study for the first time that increased plasma furin levels in a middleaged cohort are associated with elevated cancer mortality during long-term follow-up.…”

Section: Discussioncontrasting

confidence: 93%

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

et al. 2018

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BackgroundDiabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality.ObjectivesTo test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality.MethodsOvernight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population‐based prospective Malmö Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3–21.7 years follow‐up.ResultsAn association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (|0.11| ≤ β ≤ |0.31|, P < 0.001). Plasma furin (hazard ratio [HR] per one standard deviation increment of furin) was predictive of future diabetes mellitus (727 events; HR = 1.24, CI = 1.14–1.36, P < 0.001) after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive treatment, alcohol intake and fasting plasma level of glucose, insulin and lipoproteins cholesterol. Furin was also independently related to the risk of all‐cause mortality (1229 events; HR = 1.12, CI = 1.05–1.19, P = 0.001) after full multivariable adjustment.ConclusionIndividuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality.

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Section: Discussioncontrasting

confidence: 93%

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

et al. 2018

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“…This discovery was consistent with our finding that FURIN was a negative indicator for CC. Furthermore, it was reported that FURIN could predict survival in ovarian cancer 31 and might be seemed as a prognostic marker and therapeutic target for cancer 32‐34 . These studies might provide further evidence for our findings that the five genes were associated with poor prognosis.…”

Section: Discussionsupporting

confidence: 79%

A five‐mRNA signature associated with post‐translational modifications can better predict recurrence and survival in cervical cancer

et al. 2020

J Cellular Molecular Medi

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High mortality of patients with cervical cancer (CC) stresses the imperative of prognostic biomarkers for CC patients. Additionally, the vital status of post‐translational modifications (PTMs) in the progression of cancers has been reported by numerous researches. Therefore, the purpose of this research was to dig a prognostic signature correlated with PTMs for CC. We built a five‐mRNA (GALNTL6, ARSE, DPAGT1, GANAB and FURIN) prognostic signature associated with PTMs to predict both disease‐free survival (DFS) (hazard ratio [HR] = 3.967, 95% CI = 1.985‐7.927; P < .001) and overall survival (HR = 2.092, 95% CI = 1.138‐3.847; P = .018) for CC using data from The Cancer Genome Atlas database. Then, the robustness of the signature was validated using GSE44001 and the Human Protein Atlas (HPA) database. CIBERSORT algorithm analysis displayed that activated CD4 memory T cell was also an independent indicator for DFS (HR = 0.426, 95% CI = 0.186‐0.978; P = .044) which could add additional prognostic value to the signature. Collectively, the PTM‐related signature and activated CD4 memory T cell can provide new avenues for the prognostic predication of CC. These findings give further insights into effective treatment strategies for CC, providing opportunities for further experimental and clinical validations.

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“…The proprotein convertase furin not only is essential for activation of certain viruses such as HPV (Richards et al., ; Schiller et al., ) but also promotes cancer development and metastasis (Jaaks & Bernasconi, ). HPV‐induced cancers mostly occur in the cervix and oropharynx.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus endopeptidases promote HPV infection in vitro

et al. 2018

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Both cervical and throat cancers are associated with human papillomavirus (HPV). HPV infection requires cleavage of the minor capsid protein L2 by furin. While furin is present in the vaginal epithelium, it is absent in oral epithelial basal cells where HPV infection occurs. The objective of this study was to investigate whether common oral bacteria express furin‐like peptidases. By screening strains representing 12 oral Streptococcus and Enterococcus species, we identified that eight Streptococcus strains displayed high levels of furin‐like peptidase activity, with S. gordonii V2016 the highest. We constructed null mutations for 14 genes encoding putative endopeptidases in S. gordonii V2016. Results showed that three endopeptidases, PepO, PulO, and SepM, had furin‐like activities. All three mutants showed decreased natural transformation by chromosomal DNA, while the pepO mutant also showed reduced transformation by plasmid DNA, indicating involvement of these endopeptidases in competence development. The purified S. gordonii PepO protein promoted infection of epithelial 293TT cells in vitro by HPV16 pseudovirus. In conclusion, oral bacteria might promote HPV infection and contribute to HPV tissue tropism and subsequent carcinogenesis in the oral cavity and throat by providing furin‐like endopeptidases.

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The proprotein convertase furin in tumour progression

Cited by 115 publications

References 124 publications

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

A five‐mRNA signature associated with post‐translational modifications can better predict recurrence and survival in cervical cancer

Streptococcus endopeptidases promote HPV infection in vitro

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