S100A6 (calcyclin) deficiency induces senescence‐like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblasts

Abstract

S100A6 (calcyclin) is a calcium binding protein with two EF-hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non-transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by beta-galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function.

Elevated S100A6 (calcyclin) enhances tumorigenesis and suppresses CXCL14-induced apoptosis in clear cell renal cell carcinoma

“…S100A6 silencing induced G2/M phase arrest to suppress cell proliferation, which was also supported by previous studies showing that S100A6 depletion in endothelial cells increased the proportion of G2/M phase of the cell cycle [26]. However, in the NIH 3T3 fibroblasts cells, the depletion of S100A6 blocked the G0/G1 phase [27], Thus, S100A6 may have tissue-specific function in different type of cells. In this study, overexpression of S100A6 did not promote the proliferation.…”

S100A6 Regulates Endothelial Cell Cycle Progression by Attenuating Antiproliferative Signal Transducers and Activators of Transcription 1 Signaling

“…Similar phenotypes were observed both in fibroblasts and cancerous cells. 19, 34, 35 The underlying molecular pathways, however, by which S100A6 might affect EC proliferation remained elusive.…”

S100A6 expression in keratinocytes and its impact on epidermal differentiation

“…Cell differentiation was induced by increasing calcium concentration to 1.8 mM. Stably transfected HaCaT cells with either unchanged (control cells) or knocked-down level of S100A6 (S100A6 KD cells) were obtained as described earlier for fibroblasts (Słomnicki and Leśniak, 2010). HaCaT cells overexpressing S100A6 (S100A6 OE cells) were obtained by transfection with pcDNA3.1-S100A6 plasmid (Spiechowicz et al, 2007) and selection on G418.…”

“…Unsurprisingly, increased S100A6 level is observed in many cancers of epithelial origin and is usually synonymous to poor prognosis (reviewed in Leśniak et al, 2009). On the other hand, S100A6 deficiency slows down proliferation by blocking the cell cycle G1 to S phase transition and may induce cell senescence (Słomnicki and Leśniak, 2010). Despite the pronounced impact of S100A6 imbalance observed in cellular models its presumably important biological role has never been verified at the tissue or organismal level.…”