S100A6 (calcyclin) enhances the sensitivity to apoptosis via the upregulation of caspase‐3 activity in Hep3B cells

Abstract

S100A6 (calcyclin) is a small calcium-binding protein which has been implicated in several cellular processes such as cell cycle progression, cytoskeleton rearrangement, and exocytosis. Also the upregulation of S100A6 has been reported in a variety of tumors and linked to metastasis. However, exact intracellular roles of S100A6 related with apoptosis have not been clarified yet. Here we demonstrated that the upregulation of S100A6 enhances the cell death rate compared to the control under the apoptotic conditions. In exogenously S100A6 induced Hep3B cells, cell viability was significantly decreased compared with mock and S100A6-knockdown cells under calcium ionophore A23187 treatment. The exogenously introduced S100A6 significantly affected the caspase-3-like activity in programmed cell death through the enhanced caspase-3 expression, which was verified by promoter assay in wild or mutant S100A6-transfected Hep3B cells. Next, the promoter activity of caspase-3 was increased by 2.5-folds in wild-type S100A6-transfected cells compared to mutant 2 (E67K, mutant of EF-hand motif) or control. Our results suggest that S100A6 might be involved in the processing of apoptosis by modulating the transcriptional regulation of caspase-3.

Expression of S100A6 in Cardiac Myocytes Limits Apoptosis Induced by Tumor Necrosis Factor-α

“…In agreement with our observation that S100A6 is an anti-apoptotic gene, in a cholesteatoma cell line, high levels of S100A6 were associated with the lowest levels of apoptosis (11). However, several recent publications have shown that exogenously administered S100A6 at micromolar concentrations induces glioblastoma cell apoptosis by interacting with the receptor for advanced glycation end products (47), and exogenously introduced S100A6 to a human liver cell line (Hep3B and HepG2) potentiated apoptotic response of the calcium ionophore A23187 (48). These data demonstrate that the differential effects of S100A6 on apoptosis may be dependent on the specific cell type, the concentration of S100A6, and the preferential activation of one distinct signaling pathway as has been suggested for S100B (47,49).…”

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

“…However, we have noticed that the clone formation efficiency was lower in ADAR1-knockdown H9 cells than that in control cells (Supplementary information, Figure S1F). RNA-seq and RT-qPCR results further revealed that some key pro-apoptotic genes, such as S100A6 and BAX [31][32][33], were upregulated and the anti-apoptotic gene SFRP1 [34,35] was downregulated in ADAR1-knockdown H9 cells (Supplementary information, Figure S1G and Table S2), suggesting that ADAR1 deficiency can promote apoptosis of hESCs under certain stresses, such as enzymatic detachment. This is consistent with a previous report that cells cultured from ADAR1-deficient embryos exhibited increased apoptosis when a stress response was induced [24].…”

Apigenin inhibits growth and induces apoptosis in human cholangiocarcinoma cells

“…These two proteins are members of the S100 protein family and have been revealed to serve important roles in a number of tumorigenic processes, including apoptosis, cell differentiation, cell growth and cell cycle. The upregulation of S100-A6 has been demonstrated to enhance apoptosis and decrease cell viability by affecting caspase-3 activity in hepatocellular carcinoma cells (32). S100-A11 was identified to be involved in cell differentiation, cell cycle, cell growth and cell apoptosis processes.…”