Decreased expression of S100A6 in oral squamous cell carcinoma

Zhong, Yi

doi:10.3892/or_00000882

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…However, the expression and role of S100A6 in cancer cells have not been extensively studied [ 32 ]. It has been reported that S100A6 is over-expressed and associated with disease development and malignant progression in gastric cancer [ 33 ], pancreatic cancer [ 34 ], and colon cancer [ 35 ] but under-expressed in prostate cancer [ 36 ] and oral cancer [ 37 ]. However, the expression of S100A6 in breast cancer is not yet conclusive.…”

Section: Discussionmentioning

confidence: 99%

S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy

Yue

et al. 2023

Breast Cancer Res

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Background S100A6 and murine double minute 2 (MDM2) are important cancer-related molecules. A previous study identified an interaction between S100A6 and MDM2 by size exclusion chromatography and surface plasmon resonance experiments. The present study investigated whether S100A6 could bind to MDM2 in vivo and further explored its functional implication. Methods Co-immunoprecipitation, glutathione-S-transferase pull-down assay, and immunofluorescence were performed to determine the in vivo interaction between S100A6 and MDM2. Cycloheximide pulse-chase assay and ubiquitination assay were performed to clarify the mechanism by which S100A6 downregulated MDM2. In addition, clonogenic assay, WST-1 assay, and flow cytometry of apoptosis and the cell cycle were performed and a xenograft model was established to evaluate the effects of the S100A6/MDM2 interaction on growth and paclitaxel-induced chemosensitivity of breast cancer. The expressions of S100A6 and MDM2 in patients with invasive breast cancer were analyzed by immunohistochemistry. In addition, the correlation between the expression of S100A6 and the response to neoadjuvant chemotherapy was statistically analyzed. Results S100A6 promoted the MDM2 translocation from nucleus to cytoplasm, in which the S100A6 bound to the binding site of the herpesvirus-associated ubiquitin-specific protease (HAUSP) in MDM2, disrupted the MDM2–HAUSP–DAXX interactions, and induced the MDM2 self-ubiquitination and degradation. Furthermore, the S100A6-mediated MDM2 degradation suppressed the growth of breast cancer and enhanced its sensitivity to paclitaxel both in vitro and in vivo. For patients with invasive breast cancer who received epirubicin and cyclophosphamide followed by docetaxel (EC-T), expressions of S100A6 and MDM2 were negatively correlated, and high expression of S100A6 suggested a higher rate of pathologic complete response (pCR). Univariate and multivariate analyses showed that the high expression of S100A6 was an independent predictor of pCR. Conclusion These results reveal a novel function for S100A6 in downregulating MDM2, which directly enhances sensitivity to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy

Yue

et al. 2023

Breast Cancer Res

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“…Since there have only been a handful of relevant studies to date, we classify them here. Western blot analysis and realtime PCR results have shown that S100A6 protein and mRNA levels are reduced in vitro and in vivo upon carcinogenesis of oral squamous cell carcinoma (OSCC) [90]. Doxorubicin has been shown to induce the expression of miR-21-5p in mesenchymal stem cells and their derived exosomes (MSC-Exo) and then regulates S100A6 to induce breast cancer cell resistance to chemotherapy [91].…”

Section: S100a6 In Other Tumorsmentioning

confidence: 99%

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential

Yang

Zhu

et al. 2023

Biomolecules

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S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases.

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Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa

Tyszkiewicz

Jarząb

Szymczyk

et al. 2014

Folia Histochem Cytobiol.

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Epidermal differentiation complex (EDC) comprises a number of genes associated with human skin diseases including psoriasis, atopic dermatitis and hyperkeratosis. These genes have also been linked to numerous cancers, among them skin, gastric, colorectal, lung, ovarian and renal carcinomas. The involvement of EDC components encoding S100 proteins, small proline-rich proteins (SPRRs) and other genes in the tumorigenesis of head and neck squamous cell cancer (HNSCC) has been previously suggested. The aim of the study was to systematically analyze the expression of EDC components on the transcript level in HNSCC. Tissue specimens from 93 patients with HNC of oral cavity and 87 samples from adjacent or distant grossly normal oral mucosa were analyzed. 48 samples (24 tumor and 24 corresponding surrounding tissue) were hybridized to Affymetrix GeneChip Human 1.0 ST Arrays. For validation by quantitative real-time PCR (QPCR) the total RNA from all www.fhc.viamedica.pl 180 samples collected in the study was analyzed with Real-Time PCR system and fluorescent amplicon specific--probes. Additional set of samples from 14 patients with laryngeal carcinoma previously obtained by HG-U133 Plus 2.0 microarray was also included in the analyses. The expression of analyzed EDC genes was heterogeneous. Two transcripts (S100A1 and S100A4) were significantly down-regulated in oral cancer when compared to normal mucosa (0.69 and 0.36-fold change, respectively), showing an opposite pattern of expression to the remaining S100 genes. Significant up-regulation in tumors was found for S100A11, S100A7, LCE3D, S100A3 and S100A2 genes. The increased expression of S100A7 was subsequently validated by QPCR, confirming significant differences. The remaining EDC genes, including all encoding SPRR molecules, did not show any differences between oral cancer and normal mucosa. The observed differences were also assessed in the independent set of laryngeal cancer samples, confirming the role of S100A3 and LCE3D transcripts in HNC. In HNC of oral cavity only one family of EDC genes (S100 proteins) showed significant cancer-related differences. A number of other transcripts which showed altered expression in HNC require further validation.

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Decreased expression of S100A6 in oral squamous cell carcinoma

Cited by 4 publications

References 34 publications

S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy

S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential

Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa

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