S100A8 and S100A9, both transcriptionally regulated by PU.1, promote epithelial-mesenchymal transformation (EMT) and invasive growth of dermal keratinocytes during scar formation post burn

Xu, Zhigang; Cheng, Chuantao; Kong, Ranran; Liu, Yale; Wang, Shuang; Ma, Yuefeng; Xing, Xin

doi:10.18632/aging.203112

Cited by 15 publications

(7 citation statements)

References 27 publications

(27 reference statements)

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“…4 E, Table s2). S100A9 has been proved to be transcriptionally regulated by PU.1 and AP-1, which was in concordance with our finding that the PU.1-related gene SPIB and AP-1 transcription factor FOSL1 were differentially expressed in S100A9-high group (Table s2) [ 44 , 45 ]. Notably, ESR1, the estrogen receptor coding gene, was among the overexpressed TFs in S100A9-low group, which further validated that estrogen receptor signaling could contribute to immune suppression [ 46 ].…”

Section: Resultssupporting

confidence: 91%

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer

Liu,

Li,

Fang

et al. 2024

Cancer Immunol Immunother

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Background Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2−BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2−BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. Methods In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2−BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2−BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan–Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2−BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. Results By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2−BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2−BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. Conclusion In conclusion, the study we presented demonstrated that NK cells in ER+/HER2−BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

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Section: Resultssupporting

confidence: 91%

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer

Liu,

Li,

Fang

et al. 2024

Cancer Immunol Immunother

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“…3 G and H). The expressions of S100A8 and S100A9 associated with epithelial proliferation [ 30 ] were detected by qPCR. The results showed that the S100A8 and S100A9 expressions were significantly increased in IMQ group compared with the Control group (P < 0.001), while significantly decreased in the IMQ + Cap and IMQ + hDPSC groups (P < 0.001).…”

Section: Resultsmentioning

confidence: 99%

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice

Wen¹,

Li²,

Chen³

et al. 2023

Heliyon

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“…ZFP36 encodes tristetraprolin, an AU‐rich element RNA binding protein that is up‐regulated in wounded skin and controls inflammatory cytokines as well as neoplastic processes in keratinocytes (18,19). S100A2 regulates keratinocyte differentiation through its interaction with p53 (20), and expression of the alarmin S100A8 is associated with increased keratinocyte proliferation and epithelial–mesenchymal transition (21).…”

Section: Resultsmentioning

confidence: 99%

“…See Figure 1 for other definitions. keratinocyte proliferation and epithelial-mesenchymal transition (21).…”

Section: Cell-extrinsic Predictive Biomarkers Of Ssc Severitymentioning

confidence: 99%

Cell Type–Specific Biomarkers of Systemic Sclerosis Disease Severity Capture Cell‐Intrinsic and Cell‐Extrinsic Circuits

Berkowitz

Tabib

Xiao

et al. 2023

Arthritis & Rheumatology

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ObjectiveSystemic sclerosis (SSc) is a multifactorial autoimmune fibrotic disorder involving complex rewiring of cell‐intrinsic and cell‐extrinsic signaling coexpression networks involving a range of cell types. However, the rewired circuits as well as corresponding cell–cell interactions remain poorly understood. To address this, we used a predictive machine learning framework to analyze single‐cell RNA‐sequencing data from 24 SSc patients across the severity spectrum as quantified by the modified Rodnan skin score (MRSS).MethodsWe used a least absolute shrinkage and selection operator (LASSO)–based predictive machine learning approach on the single‐cell RNA‐sequencing data set to identify predictive biomarkers of SSc severity, both across and within cell types. The use of L1 regularization helps prevent overfitting on high‐dimensional data. Correlation network analyses were coupled to the LASSO model to identify cell‐intrinsic and cell‐extrinsic co‐correlates of the identified biomarkers of SSc severity.ResultsWe found that the uncovered cell type–specific predictive biomarkers of MRSS included previously implicated genes in fibroblast and myeloid cell subsets (e.g., SFPR2+ fibroblasts and monocytes), as well as novel gene biomarkers of MRSS, especially in keratinocytes. Correlation network analyses revealed novel cross‐talk between immune pathways and implicated keratinocytes in addition to fibroblast and myeloid cells as key cell types involved in SSc pathogenesis. We then validated the uncovered association of key gene expression and protein markers in keratinocytes, KRT6A and S100A8, with SSc skin disease severity.ConclusionOur global systems analyses reveal previously uncharacterized cell‐intrinsic and cell‐extrinsic signaling coexpression networks underlying SSc severity that involve keratinocytes, myeloid cells, and fibroblasts.image

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S100A8 and S100A9, both transcriptionally regulated by PU.1, promote epithelial-mesenchymal transformation (EMT) and invasive growth of dermal keratinocytes during scar formation post burn

Cited by 15 publications

References 27 publications

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice

Cell Type–Specific Biomarkers of Systemic Sclerosis Disease Severity Capture Cell‐Intrinsic and Cell‐Extrinsic Circuits

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