Unfolding the cascade of SERPINA3: Inflammation to cancer

Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188760. doi: 10.1016/j.bbcan.2022.188760. Epub 2022 Jul 16.

Abstract

SERine Protease INhibitor clade A member 3 (SERPINA3), a member of the SERine-Protease INhibitor (SERPIN) superfamily, principally works as a protease inhibitor in maintaining cellular homeostasis. It is a matricellular acute-phase glycoprotein that appears to be the sole nuclear-binding secretory serpin. Several studies have emerged in recent years demonstrating its link to cancer and disease biology. SERPINA3 seems to have cancer- and compartment-specific biological functions, acting either as a tumour promoter or suppressor in different cancers. However, the localization, mechanism of action and the effectors of SERPINA3 in physiological and pathological scenarios remain obscure. Our review aims to consolidate the current evidence of SERPINA3 in various cancers, highlighting its association with the cancer hallmarks and ratifying its status as an emerging cancer biomarker. The elucidation of SERPINA3-mediated cancer progression and its targeting might shed light on the realm of cancer therapeutics.

Keywords: Biomarker; Hallmarks of cancer; IL-6; Inflammation; JAK-STAT; Oncostatin-M; Prognosis; SERPINA3.

Publication types

  • Review

MeSH terms

  • Acute-Phase Proteins
  • Biomarkers, Tumor / genetics
  • Carcinogens
  • Humans
  • Inflammation
  • Neoplasms*
  • Serine
  • Serine Proteinase Inhibitors / therapeutic use
  • Serpins* / genetics

Substances

  • Acute-Phase Proteins
  • Biomarkers, Tumor
  • Carcinogens
  • SERPINA3 protein, human
  • Serine Proteinase Inhibitors
  • Serpins
  • Serine