S100 family signaling network and related proteins in pancreatic cancer (Review)

Abstract

Abstract. The occurrence and development of pancreatic cancer is a complex process convoluted by multi-pathogenies, multi-stages and multi-factors. S100 proteins are members of the S100 family that regulate multiple cellular pathways related to pancreatic cancer progression and metastasis. S100 proteins have a broad range of intracellular and extracellular functions, including the regulation of protein phosphorylation and enzyme activity, calcium homeostasis and the regulation of cytoskeletal components and transcriptional factors. S100 proteins interact with receptor for advanced glycation end-products (RAGE), p53 and p21, which play a role in the degradation of the extracellular matrix (ECM) and metastasis, and also interact with cytoskeletal proteins and the plasma membrane in pancreatic cancer progression and metastasis. S100A11 and S100P are significant tumor markers for pancreatic cancer and unfavorable predictors for the prognosis of patients who have undergone surgical resection. Recently, S100A2 has been suggested to be a negative prognostic biomarker in pancreatic cancer, and the expression of S100A6 may be an independent prognostic impact factor. The expression of S100A4 and S100P is associated with drug resistance, differentiation, metastasis and clinical outcome. This review summarizes the role and significance of the S100 family signaling network and related proteins in pancreatic cancer.

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

“…In colon cancer cells elevated S100P stimulated RAGE, AP-1 and induced oncogenic miR-155 and S100P-induced proliferation, motility and invasion may have been blocked either by anti-RAGE antibodies, or miR-155 knockdown 60 . In pancreatic cancer, the expression of S100A4 and S100P was associated with drug resistence, differentiation, metastasis and clinical outcome and S100A11 and S100P, and possibly also S100A2 and S100A6 were related to the unfavorable outcome of the patients after surgical resection 61 . S100A7/psoriasin was highly expressed in high-grade ductal breast carcinoma in situ 62 , high-grade comedo ductal carcinoma in situ with higher risk of local recurrence 63 and in invasive estrogen receptor negative breast cancer 64 .…”

“…23,24,39,57,61 ) Kidney cancer EN-RAGE related to obesity status in renal cancer, upregulated in tumor tissue of clear cell renal cancer, especially in pts with poorer overall survival and related to obesity status, Ala111Glu polymorphism linked to clear cell renal cancer (ref. 40,71 )…”

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

“…113,115 This is likely because S100A4 interacts with F-actin, non-muscle myosin heavy chain (NMMHC) IIA, tubulin, and non-muscle tropomyosin to increase cell migration through force generation as well as forming and stabilizing lamellipodia. 106,108,[111][112][113]116 Removal of S100A4 from cells results in increased assembly of non-muscle myosin IIA complexes, while overexpression results in large lamellipodia with a loss of focal adhesion maturation and filopodia. 112 S100A4 also interacts with Rhotekin, a Rho binding and regulating protein that participates in actin-based contractility during migration and invasion.…”

The Role of Receptors for Advanced Glycation End Product in Pancreatic Carcinogenesis

“…RAGE and S100 protein play important roles in the progression of PDA [55]. Indeed, S100 proteins interact with RAGE, which play a role in the degradation of the extracellular matrix facilitating the metastasis of pancreatic cancer [57]. AGE and RAGE are expressed in many tissues and cell types [58].…”