Elevated S100A6 (calcyclin) enhances tumorigenesis and suppresses CXCL14-induced apoptosis in clear cell renal cell carcinoma

Lyu, Xiangjun; Li, Hongzhao; Ma, Xin; Li, Xintao; Gao, Yu; Ni, Dong; Shen, Donglai; Gu, Liangyou; Wang, Baojun; Zhang, Yu; Zhang, Xu

doi:10.18632/oncotarget.3169

Cited by 28 publications

(19 citation statements)

References 38 publications

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“…Increased expression of S100A6 has been reported to be related to the progression and invasive process of several human carcinomas4243444546. Elevated expression of S100A6 protein is an independent prognostic marker in gastric cancer and pancreatic cancer patients4344.…”

Section: Discussionmentioning

confidence: 99%

Distinct prognostic values of S100 mRNA expression in breast cancer

Zhang

Wang

Liu

et al. 2017

Sci Rep

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S100 family genes encode low molecular weight, acidic-Ca2+ binding proteins implicating in a wide spectrum of biological processes. S100 family contains at least 20 members, most of which are frequently dysregulated in human malignancies including breast cancer. However, the prognostic roles of each individual S100, especially the mRNA level, in breast cancer patients remain elusive. In the current study, we used “The Kaplan-Meier plotter” (KM plotter) database to investigate the prognostic values of S100 mRNA expression in breast cancer. Our results indicated that high mRNA expression of S100A8, S100A9, S100A11 and S100P were found to be significantly correlated to worse outcome, while S100A1 and S100A6 were associated with better prognosis in all breast cancer patients. We further assessed the prognostic value of S100 in different intrinsic subtypes and clinicopathological features of breast cancer. The associated results will elucidate the role of S100 in breast cancer and may further lead the research to explore the S100-targeting reagents for treating breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Distinct prognostic values of S100 mRNA expression in breast cancer

Zhang

Wang

Liu

et al. 2017

Sci Rep

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“…CXCL14 may also induce tumor suppression in other cancers beyond HPV-positive cancers, as CXCL14 expression is downregulated in several cancers including renal and gastric cancers [18,19]. Indeed, restoration of CXCL14 expression triggers tumor suppression in lung and colorectal cancers, as well as HNC [44,48,49].…”

Section: Discussionmentioning

confidence: 99%

“…Chemokine (C-X-C motif) ligand 14 (CXCL14) is a homeostatic chemokine that promotes immune surveillance of skin epithelia through recruitment of several immune cell types, including dendritic cells (DCs), natural killer (NK) cells, and T cells [15][16][17]. Downregulation of CXCL14 expression is frequently observed in several cancers including HPV-positive cancers [18,19]. Previously, we have shown that the HPV oncoprotein E7 is responsible for the epigenetic repression of CXCL14 transcription in HPVpositive keratinocytes and cancer cells [17].…”

Section: Introductionmentioning

confidence: 99%

CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression

et al. 2019

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Evasion of the host immune responses is critical for both persistent human papillomavirus (HPV) infection and associated cancer progression. We have previously shown that expression of the homeostatic chemokine CXCL14 is significantly downregulated by the HPV oncoprotein E7 during cancer progression. Restoration of CXCL14 expression in HPV-positive head and neck cancer (HNC) cells dramatically suppresses tumor growth and increases survival through an immunedependent mechanism in mice. Although CXCL14 recruits natural killer (NK) and T cells to the tumor microenvironment, the mechanism by which CXCL14 mediates tumor suppression through NK and/or T cells remained undefined. Here we report that CD8 + T cells are required for CXCL14-mediated tumor suppression. Using a CD8 + T-cell receptor transgenic model, we show that the CXCL14-mediated antitumor CD8 + T-cell responses require antigen specificity. Interestingly, CXCL14 expression restores major histocompatibility complex class I (MHC-I) expression on HPV-positive HNC cells downregulated by HPV, and knockdown of MHC-I expression in HNC cells results in loss of tumor suppression even with CXCL14 expression. These results suggest that CXCL14 enacts antitumor immunity through restoration of MHC-I expression on tumor cells and promoting antigen-specific CD8 + T-cell responses to suppress HPV-positive HNC.

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“…We identified 4 (COL1A1, NDUFA4L2, S100A6, MT2A) out of the 223 different genes that were regulated by hypertonicity in rats and subsequently defined our OSM score based on these four genes ( Figure S1). Interestingly, all four genes have previously been associated with ccRCC tumorigenesis [9][10][11][12].…”

Section: Figure 1 (A)mentioning

confidence: 99%

Hypertonicity-Affected Genes Are Differentially Expressed in Clear Cell Renal Cell Carcinoma and Correlate with Cancer-Specific Survival

Kandabarau

Leiz

Krohn

et al. 2019

Cancers

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The heterogeneity of renal cell carcinoma (RCC) subtypes reflects the cell type of origin in the nephron, with consequences for therapy and prognosis. The transcriptional cues that determine segment-specific gene expression patterns are poorly understood. We recently showed that hypertonicity in the renal medulla regulates nephron-specific gene expression. Here, we analyzed a set of 223 genes, which were identified in the present study by RNA-Seq to be differentially expressed by hypertonicity, for the prediction of cancer-specific survival (CSS). Cluster analyses of these genes showed discrimination between tumor and non-tumor samples of clear cell RCC (ccRCC). Refinement of this gene signature to a four-gene score (OSM score) through statistical analyses enabled prediction of CSS in ccRCC patients of The Cancer Genome Atlas (TCGA) (n = 436) in univariate (HR = 4.1; 95% CI: 2.78−6.07; p = 4.39 × 10 −13 ), and multivariate analyses including primary tumor (T); regional lymph node (N); distant metastasis (M); grading (G)(p = 2.3 × 10 −5 ). The OSM score could be validated in an independent ccRCC study (n = 52) in univariate (HR = 1.29; 95% CI = 1.05-1.59; p = 0.011) and multivariate analyses (p = 0.016). Cell culture experiments using RCC cell lines demonstrated that the expression of the tumor suppressor ELF5 could be restored by hypertonicity. The innovation of our novel gene signature is that these genes are physiologically regulated only by hypertonicity, thereby providing the possibility to be targeted for therapy.

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Elevated S100A6 (calcyclin) enhances tumorigenesis and suppresses CXCL14-induced apoptosis in clear cell renal cell carcinoma

Cited by 28 publications

References 38 publications

Distinct prognostic values of S100 mRNA expression in breast cancer

Distinct prognostic values of S100 mRNA expression in breast cancer

CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression

Hypertonicity-Affected Genes Are Differentially Expressed in Clear Cell Renal Cell Carcinoma and Correlate with Cancer-Specific Survival

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