The Biological Synthesis and the Function of Mucin 2 in Pseudomyxoma Peritonei

Cancer Manag Res. 2021 Oct 15:13:7909-7917. doi: 10.2147/CMAR.S324982. eCollection 2021.

Abstract

Excessive mucus secretion is the most prominent feature of pseudomyxoma peritonei (PMP), which often leads to significant increase in abdominal circumference, intractable abdominal pain, progressive intestinal obstruction, abdominal organ adhesions, and cachexia. Excessive mucus secretion is also the main cause of death. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment for PMP. However, recurrence is frequently observed even after CRS and HIPEC, presenting similar clinical manifestations. Mucin 2 (MUC2) is the main type of mucin in PMP and plays a key role in the progressive sclerosis of mucus. To comprehensively demonstrate the biosynthetic process and molecular features of MUC2 and to provide new directions for the development of PMP mucolytic strategies, this review systematically summarizes the molecular biology of MUC2, including MUC2 gene structure, transcription, translation, post-translational modification, tertiary structure, and factors regulating mucus viscoelasticity. The results show that MUC2 is a highly glycosylated protein, with glycan accounts for 80% to 90% of the dry weight. The assembly pattern of MUC2 is highly complicated, presenting a bead-like filament. Salt concentration, pH, mucin concentration and trefoil factor family may contribute to the increase in mucus viscoelasticity and sclerosis, which could be used to develop drugs to soften or even dissolve mucus in the future.

Keywords: MUC2; biological synthesis; clinicopathologic correlation; post-translational modification; pseudomyxoma peritonei.

Publication types

  • Review

Grants and funding

General Program of the National Natural Science Foundation of China, No. 82073376; Beijing Municipal Administration of Hospitals’ Ascent Plan, No. DFL20180701.