High expression of S100A11 in pancreatic adenocarcinoma is an unfavorable prognostic marker

Xiao, Mingbing; Jiang, Feng; Ni, Wenkai; Chen, Buyou; Lu, Cuihua; Li, Xiaoyan; Ni, Runzhou

doi:10.1007/s12032-011-0058-y

Cited by 43 publications

(41 citation statements)

References 28 publications

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“…6). S100 proteins are therefore involved in the process of terminal differentiation of human epidermis and have been implicated in cancer as altered expression levels of several S100 proteins have been reported to correlate with tumor differentiation including ESCCs (7)(8)(9)(10)(11)(12)(13)(14). We have recently reported on the role of the S100 family member, S100A14, in driving esophageal carcinogenesis, showing that extracellular S100A14 affects esophageal cancer cell proliferation and apoptosis via interaction with RAGE, and intracellular S100A14 regulates cell invasion by MMP2 in a p53-dependent manner (15,16).…”

Section: Introductionmentioning

confidence: 99%

S100A14: Novel Modulator of Terminal Differentiation in Esophageal Cancer

Chen

Sunkel

et al. 2013

Molecular Cancer Research

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Aberrant keratinocyte differentiation is a key mechanism in the initiation of cancer. Because activities regulating differentiation exhibit altered or reduced capacity in esophageal cancer cells, it is vital to pinpoint those genes that control epidermal proliferation and terminal differentiation to better understand esophageal carcinogenesis. S100A14 is a member of the S100 calcium-binding protein family and has been suggested to be involved in cell proliferation, apoptosis, and invasion. The present study used immunohistochemistry analysis of S100A14 in clinical specimens of esophageal squamous cell carcinoma (ESCC) to show that decreased S100A14 is strongly correlated with poor differentiation. Furthermore, both mRNA and protein expression of S100A14 was drastically increased upon 12-O-tetra-decanoylphorbol-13-acetate (TPA) and calcium-induced esophageal cancer cell differentiation. Overexpression of S100A14 resulted in a G 1 -phase cell cycle arrest and promoted calcium-inhibited cell growth. Conversely, decreasing S100A14 expression significantly promoted G 1 -S transition and prevented the morphologic changes associated with calcium-induced cell differentiation. Molecular investigation demonstrated that S100A14 altered the calcium-induced expression of late markers of differentiation, with the most prominent effect on involucrin (IVL) and filaggrin (FLG). Finally, it was determined that S100A14 is transcriptionally regulated by JunB and that S100A14 and JunB status significantly correlated in ESCC tissue. In summary, these data demonstrate that S100A14 is transcriptionally regulated by JunB and involved in ESCC cell differentiation.

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Section: Introductionmentioning

confidence: 99%

S100A14: Novel Modulator of Terminal Differentiation in Esophageal Cancer

Chen

Sunkel

et al. 2013

Molecular Cancer Research

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“…In addition, there is evidence suggesting that SCML2 may be involved in human tumors, including malignant pediatric brain tumors, acute myeloid leukemia and human hepatocellular carcinoma (30)(31)(32)(33)(34)(35)(36). The above knowledge about SCML2, together with previous findings on SCML2 expression in islet-cell carcinoma (12)(13)(14), inspired the investigation of a more explicit linkage between SCML2 and GEP-NETs, a tumor with an increasing incidence worldwide, in the present study. SCML2 expression was detected in GEP-NET tissues using immunohistochemical staining in the present study, and then SCML2 was compared with existing markers in terms of diagnostic value.…”

Section: Discussionmentioning

confidence: 72%

“…Afterwards, sections were further reacted with mouse IgGκ binding protein-HRP (sc-516102; 1:25; Santa Cruz Biotechnology, Inc.) for 30 min at room temperature. Slides were stained with diaminobenzidine and counterstained with hematoxylin as described previously (13,14). Sections were observed under a light microscope.…”

Section: Methodsmentioning

confidence: 99%

“…SCML2 has been identified as a human gene in the Xp22 region that encodes a protein of 700 amino acids (7). In previous proteomic studies in which possible markers of pancreatic cancer were investigated (12)(13)(14), it was incidentally observed, by immunohistology, that the SCML2 protein was specifically expressed in human polypeptide hormone-producing tissues (pancreatic islet cells and islet-cell carcinoma), but was not expressed in other pancreatic epithelial cells. As a group, neuroendocrine tumors (NETs) secrete various different peptide hormones, and the aforementioned observation suggests that SCML2 could be a useful histologic marker for NETs.…”

Section: Introductionmentioning

confidence: 99%

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Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors

Yang

Huang

Xiao

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Sex comb on midleg like-2 (SCML2) is a polycomb-group protein that encodes transcriptional repressors essential for appropriate development in the fly and in mammals. On the basis of previous findings, the present study aimed to explore the possibility of developing SCML2 into a new diagnostic marker for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 64 paired GEP-NET tissues and adjacent non-tumorous tissues were obtained from patients who had undergone surgical resection between January 2009 and January 2014, and the expression of SCML2 and two neuroendocrine markers, namely synaptophysin (Syn) and chromogranin A (CgA), in the tissues was assessed by immunohistochemistry. Strong SCML2 staining was observed predominantly in the cell nuclei of GEP-NET tissues, and the overall expression rate and staining intensity of SCML2 were higher than those of Syn or CgA, respectively. Spearman rank correlation analysis demonstrated that SCML2 was not correlated with either Syn or CgA, while the combined detection of SCML2 with Syn or with CgA increased the diagnostic sensitivity to 100%. SCML2 expression in GEP-NETs was associated with several clinicopathological parameters, such as histological type, tumor grade, depth of invasion and clinical stage. Kaplan-Meier survival curves revealed that patients with higher SCML2 expression had lower survival rates than those with lower expression levels, while Cox proportional hazards regression analysis revealed that SCML2 was not an independent prognostic factor for GEP-NET patients. Therefore, SCML2 may have potential as a specific marker for joint use with other markers to improve the diagnostic efficiency of GEP-NETs.

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“…Furthermore, S100A11-RAGE interaction is correlated with the inflammation of chondrocytes (8). It has been reported that overexpression of S100A11 protein is associated with a number of cancers, including breast (9), colon (10), pancreatic (11), and papillary thyroid carcinoma (12). However, overexpression of S100A11 protein results in the contrary effect in ovarian (13) and bladder cancer (14).…”

mentioning

confidence: 99%

Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation

Huang

Chou

2016

Journal of Biological Chemistry

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The human S100 calcium-binding protein A11 (S100A11) is a member of the S100 protein family. Once S100A11 proteins bind to calcium ions at EF-hand motifs, S100A11 changes its conformation, promoting interaction with target proteins. The receptor for advanced glycation end products (RAGE) consists of three extracellular domains, including the V domain, C1 domain, and C2 domain. In this case, the V domain is the target for mutant S100A11 (mS100A11) binding. RAGE binds to the ligands, resulting in cell proliferation, cell growth, and several signal transduction cascades. We used NMR and fluorescence spectroscopy to demonstrate the interactions between mS100A11 and RAGE V domain. The tranilast molecule is a drug used for treating allergic disorders. We discovered that the RAGE V domain and tranilast would interact with mS100A11 by using 1 H-15 N HSQC NMR titrations. According to the results, we obtained two binary complex models from the HADDOCK program, S100A11-RAGE V domain and S100A11-tranilast, respectively. We overlapped two binary complex models with the same orientation of S100A11 homodimer and demonstrated that tranilast would block the binding site between S100A11 and the RAGE V domain. We further utilized a water-soluble tetrazolium-1 assay to confirm this result. We think that the results will be potentially useful in the development of new anti-cancer drugs.Human S100 proteins are a family of low molecular weight, homodimeric, and acidic proteins that contain two EF-hand motifs that can bind to calcium ions (1, 2). Human S100A11 (S100C) protein is a member of the S100 family. S100A11 was first discovered in chicken gizzards and is also called calgizzarin (3). S100A11 protein can be expressed in the heart, kidney, liver, lung, and other tissues. It is most abundant in smooth muscle tissues (4). In previous studies, it has been shown that S100A11 protein can interact with various other proteins, such as annexin A1 and A2, ATPase Rad54B, and RAGE.2 The interactions induce activities or conformational changes of these target proteins and further promote the specific physiological functions. Calcium-bound S100A11 homodimer acts as a bridge to link two N termini of annexin proteins, inducing plasma membrane vesiculation in cells (5, 6). Interaction between S100A11 and DNA repair and recombination protein Rad54B participates in the repair of double-stranded DNA and regulation of the cell cycle (7). Furthermore, S100A11-RAGE interaction is correlated with the inflammation of chondrocytes (8). It has been reported that overexpression of S100A11 protein is associated with a number of cancers, including breast (9), colon (10), pancreatic (11), and papillary thyroid carcinoma (12). However, overexpression of S100A11 protein results in the contrary effect in ovarian (13) and bladder cancer (14). Reduced expression of S100A11 protein is correlated with progression of ovarian and bladder cancer, which has been investigated in previous studies. RAGE, the receptor of the immunoglobulin for signal transductions at the cel...

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High expression of S100A11 in pancreatic adenocarcinoma is an unfavorable prognostic marker

Cited by 43 publications

References 28 publications

S100A14: Novel Modulator of Terminal Differentiation in Esophageal Cancer

S100A14: Novel Modulator of Terminal Differentiation in Esophageal Cancer

Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors

Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation

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