Evolution and functions of stanniocalcins in cancer.

Stanniocalcin (STC), first isolated from the corpuscles of stannius of teleost fishes, was originally known for its regulation on calcium/phosphate transport. Increasing evidence demonstrates that STCs display the important function in some physiological and pathological behaviors such as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, nerve diseases, etc. Moreover, STCs are implicated in the development and progression of multiple malignancies through promoting cell growth, proliferation, invasion, metastasis, and apoptotic escape. Some studies have shown that NF-κB upregulates STC expression, thereby activating the downstream HIF-1/ERK1/2 signaling pathway, enhancing the transcriptional activity of tumor-related factors (MMP-2/9, cyclinD1, Bcl-2, N-cadherin, etc) and contributing to tumorigenesis. Here, this brief review describes recent progress of STCs in mammalians, focused mainly on their critical functions in cancer.

IL-10 treatment is associated with prohibitin expression in the Crohn's disease intestinal fibrosis mouse model.

Prohibitin, which can inhibit oxidative stress and mitochondrial dysfunction, has been shown to have significant anti-inflammatory activities. Here, we investigate the effects of altering prohibitin levels in affected tissues in the interleukin-10 knockout (IL-10KO) mouse model with intestinal fibrosis. The aim of this study is to investigate the effects of IL-10 on prohibitin and the role of prohibitin in intestinal fibrosis of murine colitis. After the mice were treated with IL-10, prohibitin expression and localization were evaluated in IL-10KO and wild-type (WT, 129/SvEv) mice. The colon tissue was then investigated and the potential pathogenic molecular mechanisms were further studied. Fluorescence-based quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry assays revealed a significant upregulation of prohibitin with IL-10 treatment. Furthermore, IL-10 decreases inflammatory cytokines and TGF-ß1 in the IL-10KO model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. In conclusion, we hypothesize that IL-10 treatment is associated with increased prohibitin and would decrease inflammation and fibrosis in an animal model of Crohn's disease. Interestingly, prohibitin may be a potential target for intestinal fibrosis associated with inflammatory bowel disease (IBD).

Clinicopathologic characteristics of YES-associated protein 1 overexpression and its relationship to tumor biomarkers in gastric cancer.

Yes-associated protein 1 (YAP1), a downstream effector of the Hippo pathway, plays an important role in the development and progression of multiple malignancies, including human gastric cancer (GC). However, the clinical significance of YAP1 expression in GC needs to be comprehensively explored. Based on the pivotal role of YAP1 in the hippo pathway, we explored the clinicopathologic characteristics of YAP1 overexpression and its relationship to some tumor biomarkers in GC. Ninety cases of GC, chronic gastritis (CG) and CG with dysplasia samples were collected, and clinical data of all patients with GC were analyzed. The expression of YAP1 was assessed using immunohistochemical assay in biopsy samples. As a result, almost all the GC samples, but few CG and dysplasia samples showed YAP1 positive staining mainly in the nucleus. The expression of YAP1 was found in GC tissues with higher strong reactivity rate, compared with dysplasia and CG tissues (79.2 percent vs 47.1 percent and 15 percent, each P<0.001), and its expression level was elevated with the ascending order of GC malignancy. However, no significant correlation was found between the expression of YAP1 and epidermal growth factor receptor (EGFR) with gender, age, gross stage, degree of differentiation, tumor size, TNM staging, perineural infiltration, vascular invasion, lymphatic vessel invasion and lymph node metastases in patients with GC (each P>0.05). Furthermore, Spearman rank correlation analysis also showed no correlation of YAP1 with EGFR, Ki-67, CD34 and topoisomerase II (TOP II). Taken together, YAP1 is highly expressed in GC tissues compared with the dysplasia and CG tissues and its expression level is elevated with the ascending order of tumor malignancy; but, YAP1 expression does not correlate with the clinicopathologic characteristics and the expression of EGFR, Ki-67, CD34 and TOP II in GC.

Expression of Yes-associated protein in gastric adenocarcinoma and inhibitory effects of its knockdown on gastric cancer cell proliferation and metastasis.

Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels of YAP, proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown of YAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression of YAP was observed in 69.23 percent gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through down-regulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.

Identification of differentially-expressed proteins between early submucosal non-invasive and invasive colorectal cancer using 2D-DIGE and mass spectrometry.

Early detection and diagnosis of colorectal cancer (CRC) are closely related to a better therapeutic outcome, and the five-year survival rate of early CRC is over 90 percent. Though endoscopic minimally invasive treatment has become a quick and effective therapy for early CRC, endoscopic biopsies are usually not deep enough to obtain tissues from the submucosal layer and it is difficult to determine whether early CRC has infiltrated into the submucosa. Therefore, in the present study, we constructed tumor models of early submucosal non-invasive CRC (SNICRC) and submucosal invasive CRC (SICRC) in Fischer-344 rats induced by N-methyl-N-nitrosourea (MNU). The differentially-expressed proteins were analyzed and identified in SNICRC, SICRC and normal control (NC) tissues using highly sensitive two dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Proteomic data revealed 132 protein spots between SNICRC and SICRC, 162 protein spots between SICRC and NC and 154 protein spots between SNICRC and NC which were found differentially expressed. These differential spots were picked, in-gel digested and peptide mass fingerprints were obtained by MALDITOF-MS/MS. Finally, five differentially-expressed proteins in SNICRC, SICRC and NC were identified, and increases in Transgelin, peptidylprolyl isomerase A (PPIA) and tropomyosin alpha isoform d were observed, while decreases in carbonic anhydrase 2 (CAII) and an unnamed protein were detected in SICRC compared with SNICRC and NC. Furthermore, Fluorescence-based quantitative polymerase chain reaction (FQ-PCR), Western blotting and immunohistochemistry assays also revealed significant upregulation of Transgelin expression and down-regulation of CAII expression in SICRC tissues. In conclusion, 2D-DIGE is confirmed to be an efficient strategy that enables us to identify differentially expressed proteins between early SNICRC and SICRC. The potential biomarkers such as Transgelin and CAII may be used for the detection of early SICRC.