The possible role furin and furin inhibitors in endometrial adenocarcinoma: A narrative review

Author:

Al‐kuraishy Hayder M.1,Al‐Maiahy Thabat J.2,Al‐Gareeb Ali I.1,Alexiou Athanasios3456ORCID,Papadakis Marios7,Saad Hebatallah M.8ORCID,Batiha Gaber El‐Saber9

Affiliation:

1. Department of Clinical Pharmacology and Medicine College of Medicine, Mustansiriyah University Baghdad Iraq

2. Department of Gynecology and Obstetrics College of Medicine, Mustansiriyah University Baghdad Iraq

3. University Centre for Research & Development Chandigarh University, Chandigarh‐Ludhiana Highway Mohali Punjab India

4. Department of Research & Development Funogen Athens Greece

5. Department of Research & Development AFNP Med Wien Austria

6. Department of Science and Engineering Novel Global Community Educational Foundation Hebersham New South Wales Australia

7. Department of Surgery II University Hospital Witten‐Herdecke, University of Witten‐Herdecke Wuppertal Germany

8. Department of Pathology Faculty of Veterinary Medicine, Matrouh University Matrouh Egypt

9. Department of Pharmacology and Therapeutics Faculty of Veterinary Medicine, Damanhour University Damanhour AlBeheira Egypt

Abstract

AbstractBackgroundEndometrial adenocarcinoma (EAC) is a malignant tumor of the endometrium. EAC is the most common female malignancy following the menopause period. About 40% of patients with EAC are linked with obesity and interrelated with hypertension, diabetes mellitus, and high circulating estrogen levels. Proprotein convertase (PC) furin was involved in the progression of EAC.Recent findingsFurin is a protease enzyme belonging to the subtilisin PC family called PC subtilisin/kexin type 3 that converts precursor proteins to biologically active forms and products. Aberrant activation of furin promotes abnormal cell proliferation and the development of cancer. Furin promotes angiogenesis, malignant cell proliferation, and tissue invasion by malignant cells through its pro‐metastatic and oncogenic activities. Furin activity is correlated with the malignant proliferation of EAC. Higher expression of furin may increase the development of EAC through overexpression of pro‐renin receptors and disintegrin and metalloprotease 17 (ADAM17). As well, inflammatory signaling in EAC promotes the expression of furin with further propagation of malignant transformation.ConclusionFurin is associated with the development and progression of EAC through the induction of proliferation, invasion, and metastasis of malignant cells of EAC. Furin induces ontogenesis in EAC through activation expression of ADAM17, pro‐renin receptor, CD109, and TGF‐β. As well, EAC‐mediated inflammation promotes the expression of furin with further propagation of neoplastic growth and invasion.

Publisher

Wiley

Subject

Cancer Research,Oncology

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