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Review
. 2023 Sep 5;11(1):78.
doi: 10.1186/s40364-023-00515-3.

S100A6: molecular function and biomarker role

Yidian Wang  1 , Xuewen Kang  2   3   4 , Xin Kang  5 , Fengguang Yang  6   7   8   9
Affiliations
Review

S100A6: molecular function and biomarker role

Yidian Wang et al. Biomark Res. .

Abstract

S100A6 (also called calcyclin) is a Ca2+-binding protein that belongs to the S100 protein family. S100A6 has many functions related to the cytoskeleton, cell stress, proliferation, and differentiation. S100A6 also has many interacting proteins that are distributed in the cytoplasm, nucleus, cell membrane, and outside the cell. Almost all these proteins interact with S100A6 in a Ca2+-dependent manner, and some also have specific motifs responsible for binding to S100A6. The expression of S100A6 is regulated by several transcription factors (such as c-Myc, P53, NF-κB, USF, Nrf2, etc.). The expression level depends on the specific cell type and the transcription factors activated in specific physical and chemical environments, and is also related to histone acetylation, DNA methylation, and other epigenetic modifications. The differential expression of S100A6 in various diseases, and at different stages of those diseases, makes it a good biomarker for differential diagnosis and prognosis evaluation, as well as a potential therapeutic target. In this review, we mainly focus on the S100A6 ligand and its transcriptional regulation, molecular function (cytoskeleton, cell stress, cell differentiation), and role as a biomarker in human disease and stem cells.

Keywords: Biomarker; Cell differentiation; Cellular stress response; Cytoskeleton; S100A6; Stem cells; Tumor.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
S100A6 gene structure and transcription factors (based on literature reports)
Fig. 2
Fig. 2
S100A6 is involved in the regulation of cellular stress response. Cyp40, cyclophilin 40; Hop, Hsp90/Hsp70-organizing protein; Tom70, translocase of outer mitochondrial membrane70
Fig. 3
Fig. 3
Schematic localization of S100A2, S100A3 and S100A6. A Hair matrix cells (some S100A2 positive) proliferated and differentiated into cortical and cuticular cells (S100A3 positive), and the inner root sheath cells (S100A6 positive). Outer root sheath cells (S100A2 positive) surround the hair bulb. Co, cortex of hair; Cu, cuticle of hair; IRS, inner root sheath; ORS, outer root sheath. B Tumour island of pilomatrixoma. Basophil cells (patellar S100A2 positive) divide into adhesion shadow cells (S100A3 positive), transparent shadow cells (S100A6 positive), and possibly columnar or dispersed cuticle cells (S100A3 positive). The outer root sheath cells are inherited by squamous cells (S100A2 positive). (Adapted from reference 83)
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