S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives

Abstract

Pancreatic cancer (PC) is a highly malignant tumor occurring in the digestive system. Currently, there is a lack of specific and effective interventions for PC; thus, further exploration regarding the pathogenesis of this malignancy is warranted. The S100 protein family, a collection of calcium-binding proteins expressed only in vertebrates, comprises 25 members with high sequence and structural similarity. Dysregulated expression of S100 proteins is a biomarker of cancer progression and prognosis. Functionally, these proteins are associated with the regulation of multiple cellular processes, including proliferation, apoptosis, growth, differentiation, enzyme activation, migration/invasion, Ca2+ homeostasis, and energy metabolism. This review highlights the significance of the S100 family in the diagnosis and prognosis of PC and its vital functions in tumor cell metastasis, invasion and proliferation. A further understanding of S100 proteins will provide potential therapeutic targets for preventing or treating PC.

Keywords: S100 proteins; biomarkers; mechanisms; pancreatic cancer; therapeutic targets.

Figure 1

Summary of the potential mechanisms of several S100 proteins affecting PC. S100 proteins present in or derived from PC cells and surrounding stromal cells can play an important intracellular and extracellular role in the PC development. S100A4, S100A6, S100A7, S100A8, S100A9, S100A10, S00A11, S10016 and S100P show increased expression during PC development. They can act on certain proteins or signaling pathways inside or outside the cell, directly or indirectly affecting the growth, proliferation, metastasis or invasion of PC. However, S00A14 can inhibit PC metastasis or apoptosis of PC cells. EMT, epithelial-mesenchymal transition; ERK1/2, extracellular signal-regulated kinase 1/2; FAK, focal adhesion kinase; IL-6/11, interleukin-6/11; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PEG2, prostaglandin E2; PI3K/AKT, phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT); RAGE, advanced glycosylation end-product receptor; STAT3, signal transducer and activator of transcription 3; TGF-β1, transforming growth factor beta-1.