S100A6 as a Constituent and Potential Marker of Adult and Cancer Stem Cells

Leśniak, Wiesława

doi:10.1007/s12015-022-10403-2

Cited by 3 publications

(5 citation statements)

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“…The highest level of S100A6 expression is found in fibroblasts and epithelial cells [ 5 ], but it is also expressed in highly specialized cells such as certain neurons [ 17 ], glial cells [ 18 ], smooth or cardiac muscle cells [ 19 , 20 ] or various hematopoietic cells [ 21 , 22 ]. Interestingly, S100A6 has been detected in adult stem/progenitor cells of various lineages, e.g., in hematopoietic, neural and epidermal stem cells [ 23 ]. Single-cell RNA-seq experiments confirmed that S100A6 expression strongly correlated with the expression of established adult stem cell markers and was, in the majority of cases, characteristic for the most quiescent stem cell subpopulation.…”

Section: Localization and Expression Of S100a6mentioning

confidence: 99%

“…Differences in S100A6 level proved to also be useful for the discrimination between primary liver tumors such as hepatocellular carcinoma and metastases derived from colorectal carcinoma [ 192 , 193 ]. All these data, together with the fact that S100A6 is detected in cancer stem cells [ 23 ], point to a potential role of S100A6 in the development of malignancy. In addition, due to changes in S100A6 expression during cancer progression, the protein has been recognized as a useful diagnostic and prognostic tool for defining cancer stage and patient prognosis as, for example, in the case of pancreatic and lung adenocarcinoma [ 194 , 195 ].…”

Section: S100a6 In Various Pathologiesmentioning

confidence: 99%

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S100A6 Protein—Expression and Function in Norm and Pathology

Leśniak

Filipek

2023

IJMS

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S100A6, also known as calcyclin, is a calcium-binding protein belonging to the S100 protein family. It was first identified and purified more than 30 years ago. Initial structural studies, focused mostly on the mode and affinity of Ca2+ binding and resolution of the resultant conformational changes, were soon complemented by research on its expression, localization and identification of binding partners. With time, the use of biophysical methods helped to resolve the structure and versatility of S100A6 complexes with some of its ligands. Meanwhile, it became clear that S100A6 expression was altered in various pathological states and correlated with the stage/progression of many diseases, including cancers, indicative of its important, and possibly causative, role in some of these diseases. This, in turn, prompted researchers to look for the mechanism of S100A6 action and to identify the intermediary signaling pathways and effectors. After all these years, our knowledge on various aspects of S100A6 biology is robust but still incomplete. The list of S100A6 ligands is growing all the time, as is our understanding of the physiological importance of these interactions. The present review summarizes available data concerning S100A6 expression/localization, interaction with intracellular and extracellular targets, involvement in Ca2+-dependent cellular processes and association with various pathologies.

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Section: Localization and Expression Of S100a6mentioning

confidence: 99%

Section: S100a6 In Various Pathologiesmentioning

confidence: 99%

S100A6 Protein—Expression and Function in Norm and Pathology

Leśniak

Filipek

2023

IJMS

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“…Owing to its potential to repair tissue damage, it is the focus of tissue engineering and other regenerative repair research. However, stem cells are scarce and lack universal markers, making their isolation and identification difficult [ 30 ]. In recent years, the development of various omics technologies has helped to promote stem cell-related research.…”

Section: Biomarker Role Of S100a6mentioning

confidence: 99%

“…According to current knowledge, there are mainly two regions of neural stem cells in the brain of adult mice: the subventricular zone (SVZ) near the lateral ventricles of the forebrain, and the subgranular layer of the dentate gyrus of the hippocampal formation [ 30 ]. Some studies have shown that S100A6 is highly expressed in neural stem cells labeled with the sex-determining region Y-box 2, brain lipid-binding protein, and glial fibrillary acidic protein by immunofluorescence multiple labeling.…”

Section: Biomarker Role Of S100a6mentioning

confidence: 99%

“…S100A6 is not only expressed in cells but also secreted out of cells [ 29 ], and can be detected in various body fluids, such as the extracellular matrix and blood [ 6 ]. Therefore, the differential expression of S100A6 in specific diseases makes it a useful biomarker for disease diagnosis and differentiation [ 30 ]. This has been one of the lucrative research directions for S100A6 in recent years.…”

Section: Introductionmentioning

confidence: 99%

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S100A6: molecular function and biomarker role

Wang,

Kang,

Kang

et al. 2023

Biomark Res

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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.

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Single-cell RNA and T-cell receptor sequencing unveil mycosis fungoides heterogeneity and a possible gene signature

Srinivas,

Peiffer,

Horny

et al. 2024

Front. Oncol.

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BackgroundMycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL). Comprehensive analysis of MF cells in situ and ex vivo is complicated by the fact that is challenging to distinguish malignant from reactive T cells with certainty.MethodsTo overcome this limitation, we performed combined single-cell RNA (scRNAseq) and T-cell receptor TCR sequencing (scTCRseq) of skin lesions of cutaneous MF lesions from 12 patients. A sufficient quantity of living T cells was obtained from 9 patients, but 2 had to be excluded due to unclear diagnoses (coexisting CLL or revision to a fixed toxic drug eruption).ResultsFrom the remaining patients we established single-cell mRNA expression profiles and the corresponding TCR repertoire of 18,630 T cells. TCR clonality unequivocally identified 13,592 malignant T cells. Reactive T cells of all patients clustered together, while malignant cells of each patient formed a unique cluster expressing genes typical of naive/memory, such as CD27, CCR7 and IL7R, or cytotoxic T cells, e.g., GZMA, NKG7 and GNLY. Genes encoding classic CTCL markers were not detected in all clusters, consistent with the fact that mRNA expression does not correlate linearly with protein expression. Nevertheless, we successfully pinpointed distinctive gene signatures differentiating reactive malignant from malignant T cells: keratins (KRT81, KRT86), galectins (LGALS1, LGALS3) and S100 genes (S100A4, S100A6) being overexpressed in malignant cells.ConclusionsCombined scRNAseq and scTCRseq not only allows unambiguous identification of MF cells, but also revealed marked heterogeneity between and within patients with unexpected functional phenotypes. While the correlation between mRNA and protein abundance was limited with respect to established MF markers, we were able to identify a single-cell gene expression signature that distinguishes malignant from reactive T cells.

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S100A6 as a Constituent and Potential Marker of Adult and Cancer Stem Cells

Cited by 3 publications

References 84 publications

S100A6 Protein—Expression and Function in Norm and Pathology

S100A6 Protein—Expression and Function in Norm and Pathology

S100A6: molecular function and biomarker role

Single-cell RNA and T-cell receptor sequencing unveil mycosis fungoides heterogeneity and a possible gene signature

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