The Role of Selected Serpins in Gastrointestinal (GI) Malignancies

Abstract

Gastrointestinal (GI) cancers, which are a diverse group of malignant diseases, represent a major healthcare problem around the world. Due to the lack of specific symptoms in the early stages as well as insufficient diagnostic possibilities, these malignancies occupy the leading position in the causes of death worldwide. The currently available tests have too many limitations to be part of routine diagnostics. Therefore, new potential biomarkers that could be used as diagnostic and prognostic factors for these cancers are still being sought. Among the proteins that might fit this role are serpins, which are serine protease inhibitors. Although the serpins themselves have been known for many years, they have recently become the centre of attention for many authors, especially due to the fact that a number of proteins in this family are involved in many stages of neoplasia formation, from angiogenesis through tumour growth to progression. Therefore, the aim of this review is to present the current knowledge about the significance of serpins in GI malignancies, especially their involvement in the development and progression of oesophageal, gastric, pancreatic and colorectal cancers. This review summarises and confirms the important roles of selected serpins in the pathogenesis of various GI cancers and also points to their promising roles as therapeutic targets. However, due to the relatively nonspecific nature of serpins, future research should be carried out to elucidate the mechanisms involved in tumour pathogenesis in more detail.

Keywords: biomarkers; cancer; gastrointestinal malignancies; serine protease inhibitors; serpins.

Figure 1

The inhibitory and non-inhibitory function of serpins [43]. A1AT: alpha-1-antitripsin; AT: antithrombin; PAI-1: plasminogen activator inhibitor-1; PAI-2: plasminogen activator inhibitor-2; MASP: maspin; TBG: thyroxine binding globulin.

Figure 2

The role of PAI-1 in cancer [56].