Influence of S100A2 in Human Diseases

Sugino, Hitomi; Sawada, Yu

doi:10.3390/diagnostics12071756

Cited by 9 publications

(7 citation statements)

References 98 publications

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“…These findings are in line with previous results uncovering the role of GPC1 in tumor microenvironment modulation and interaction with growth factors, receptors and major downstream pathways that lead to tumor growth, invasion and metastasis [for review see 1,2,9,10,32]. Network reconstruction data also revealed direct interaction between GPC1 and S100A2 which is directly involved in regulation of cell cycle and differentiation via its 2 EF-hand [33]. An interaction between GPC1 and H1-3 was also suggested by network reconstruction indicating involvement of GPC1 in gene transcription.…”

Section: Figure 6: Overexpression Of Gpc1 Increases Proliferation Of ...supporting

confidence: 90%

“…Network reconstruction of the predicted relationships between molecules as inferred from gene expression changes reveal that GPC1 -low patients reveals inhibition of linchpin regulators positively associated with cancer maintenance and progression, including transforming growth factor beta 1 (TGFβ), p38 MAPK, AKT, and PDGF-BB, interferon-α and WNT [For review see 1, 9, 10, 31, 32] ( Figure 7B ). Moreover, direct interaction was predicted between GPC1 and S100A2 which encodes A2 member of the S100 proteins family, highly involved in regulation of cell cycle and differentiation via its 2 EF-hand calcium-binding motif [ 33 ]. Also, direct interaction was predicted between GPC1 and H1-3 which encodes H1.3 linker histone indicating involvement of chromatin remodeling, nucleosome spacing and DNA methylation and thereby regulation of gene transcription ( Figure 7B ).…”

Section: Resultsmentioning

confidence: 99%

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Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior

et al. 2023

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Glypicans (GPC1-6) are associated with tumorigenic processes and their involvement in neoplastic behavior has been discussed in different cancer types. Here, a cancer-wide GPC expression study, using clinical cancer patient data in The Cancer Genome Atlas, reveals net upregulation of GPC1 and GPC2 in primary solid tumors, whereas GPC3 , GPC5 and GPC6 display lowered expression pattern compared to normal tissues. Focusing on GPC1 , survival analyses of the clinical cancer patient data reveal statistically significant correlation between high expression of GPC1 and poor prognosis in 10 particular cancer types i.e., bladder urothelial carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, colon adenocarcinoma, kidney renal clear cell carcinoma, lung adenocarcinoma, mesothelioma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma and uveal melanoma. In vitro studies targeting GPC1 expression by CRISPR/Cas9 or siRNA or treatment with an anti-GPC1 antibody resulted in attenuation of proliferation of cancer cells from bladder carcinoma, glioma and hepatocellular carcinoma patients (T24, U87 and HepG2 cells). Further, overexpression of GPC1 exhibited a significant and negative correlation between GPC1 expression and proliferation of T24 cells. Attempt to reveal the mechanism through which downregulation of GPC1 leads to attenuation of tumor growth using systematic Ingenuity Pathway Analysis indicate that suppression of GPC1 results in ECM-mediated inhibition of specific pro-cancer signaling pathways involving TGF-β and p38 MAPK. Identified differential expression and pleiotropic effects of GPCs in specific cancer types emphasize their potential of as novel diagnostic tools and prognostic factors and open doors for future GPC targeted therapy.

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Section: Figure 6: Overexpression Of Gpc1 Increases Proliferation Of ...supporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior

et al. 2023

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“…ANXA1 has been implicated in the regulation of eosinophil infiltration and the production of inflammatory cytokines, which are key features of ECRSwNP. S100A2 is a calcium-binding protein known to be involved in the regulation of cell differentiation and proliferation [24][25][26]. S100A9 is another member of the S100 family of calcium-binding proteins that has been linked to the development of ECRSwNP [24].…”

Section: Discussionmentioning

confidence: 99%

“…It is involved in the regulation of inflammation and immune responses, and its upregulation has been observed in the nasal polyps of CRSwNP patients [27]. S100A9 has been shown to promote the activation of inflammatory cells and the production of cytokines and chemokines [26], which are key features of ECRSwNP. KRT5 and KRT17 are intermediate filament proteins that are expressed in epithelial cells [28].…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of immune‐related signature profiles in eosinophilic chronic rhinosinusitis with nasal polyposis

Kan,

Guan,

Hao

et al. 2023

FEBS Open Bio

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Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of chronic rhinosinusitis (CRS) that is associated with the nasal cavity and sinus polyps, elevated levels of eosinophils, and dysregulated immune responses to environmental triggers. The underlying cause of ECRSwNP is not well understood, and few studies have focused on the unique features of this subtype of CRS. Our study integrated proteomic and transcriptomic data with multi‐omic bioinformatics analyses. We collected nasal polyps from three ECRSwNP patients and three control patients and identified 360 differentially expressed proteins, including 119 up‐regulated and 241 down‐regulated proteins. Functional analyses revealed several significant associations with ECRSwNP, including focal adhesion, hypertrophic cardiomyopathy, and ECM‐receptor interactions. Additionally, a protein‐protein interaction (PPI) network revealed seven hub proteins that may play crucial roles in the development of ECRSwNP. We also compared the proteomic data with publicly available transcriptomic data, and identified a total of 1,077 differentially expressed genes. Pathways enriched by the differentially expressed genes involved angiogenesis, positive regulation of cell motility, and immune responses. Furthermore, we investigated immune cell infiltration and identified biomarkers associated with eosinophil and M2 macrophage infiltration using CIBERSORT and Weighted Gene Correlation Network Analysis (WGCNA). Our results provide a more complete picture of the immune‐related mechanisms underlying ECRSwNP, which could contribute to the development of more precise treatment strategies for this condition.

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“… 7 Calcium sensors and modulators, such as A2 (S100A2), are involved in calcium signaling within cells. 8 S100A2 is also a composed protein of keratoconus corneal proteome, co-expressed with and regulated by KRT6A. 9 Several cancer types have been found to have dysregulation of KRT6A or S100A2.…”

Section: Introductionmentioning

confidence: 99%

Sinapine thiocyanate exhibited anti-colorectal cancer effects by inhibiting KRT6A/S100A2 axis

Yang,

Zeng,

et al. 2023

Cancer Biology & Therapy

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Sinapine thiocyanate (ST), an alkaloid existed extensively in seeds of cruciferous plants, exhibits a number of pharmacological effects, including anti-inflammatory and anti-malignancy properties. However, it is still unknown what effects and molecular mechanisms ST has on colorectal cancer (CRC). In the current study, it was indicated that ST inhibited proliferation, colony formation, and apoptosis in vitro , as well as arrested the G1 phase of CRC cells. There was a significant repressive effects of ST on invasion and migration of CRC cells in vitro . RNA-sequencing indicated that 750 differentially expressed genes existed in CRC cells after ST treatment, and enrichment analysis demonstrated that ST obviously decreased the activation of keratinization pathways. Among DEGs enriched in keratinization, keratin 6A (KRT6A) was decreased the most significant, as well as its target gene S100 calcium-binding protein A2 (S100A2). Low expression of KRT6A and S100A2 signatures indicated a favorable prognosis in CRC patients. Moreover, we found overexpression of KRT6A relieved the inhibitory effects of ST in CRC cells. Furthermore, ST inhibited the CRC cell proliferation in vivo , and reduced KRT6A and KI67 expression in xenograft tumor. Taken together, we demonstrated that ST exhibited anti-CRC properties by inhibiting KRT6A/S100A2 axis. It is possible that ST can be used as a treatment for CRC.

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Influence of S100A2 in Human Diseases

Cited by 9 publications

References 98 publications

Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior

Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior

Integrative analysis of immune‐related signature profiles in eosinophilic chronic rhinosinusitis with nasal polyposis

Sinapine thiocyanate exhibited anti-colorectal cancer effects by inhibiting KRT6A/S100A2 axis

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