The importance of store-operated Ca2+ entry (SOCE) and the role of its key molecular regulators, STIM1 and ORAI1, in the development of cancer are emerging. Here, we report an unexpected dual function of SOCE in prostate cancer progression by revealing a decrease in the expression of STIM1 in human hyperplasia and tumor tissues of high histological grade and by demonstrating that STIM1 and ORAI1 inhibit cell growth by arresting the G0/G1 phase and enhancing cell senescence in human prostate cancer cells. In addition, STIM1 and ORAI1 inhibited NF-κB signaling and remodeled the tumor microenvironment by reducing the formation of M2 phenotype macrophages, possibly creating an unfavorable tumor microenvironment and inhibiting cancer development. However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-β, Snail and Wnt/β-Catenin pathways. Thus, our study revealed novel regulatory effects and the mechanisms by which STIM1 affects cell senescence, tumor migration and the tumor microenvironment, revealing that STIM1 has multiple functions in prostate cancer cells.

Since reports on the clinical significance of legumain in cancer have shown inconsistent results, we systematically evaluated clinical indicators of legumain in cancer. We searched the Cochrane Library, PubMed, Embase, and EBSCO databases and the Wangfang and CNKI databases in China by using “legumain” and (“neoplasms” OR “cancer”) as search terms. We included case-controlled studies of legumain and cancer. The quality of the studies was evaluated by using Lichtenstein’s guidelines, and valid data was extracted for analysis. In total, 10 articles were included in this study. Meta-analysis showed that legumain was overexpressed in cancer compared with in normal tissue and was higher in stage III–IV disease than in I–II disease. Moreover, legumain overexpression was correlated with poor prognosis and clinical stage. Furthermore, Cancer Genome Atlas data showed that among patients with rectal cancer, those with tumors overexpressing legumain had shorter overall survival than those in the low expression group (P < 0.05). Legumain appears to be involved in tumor development and deterioration; thus, it can potentially be developed into both a marker for monitoring and diagnosing tumors and a therapeutic target.

This study highlights the prevalence of aminoglycoside-modifying enzyme genes and virulence determinants among clinical enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. Screening for high-level aminoglycoside resistance against 117 enterococcal clinical isolates was performed using the agar-screening method. Out of the 117 enterococcal isolates, 46 were selected for further detection and determination of the distribution of aminoglycoside-modifying enzyme-encoding genes and virulence determinants using polymerase chain reaction -based methods. Enterococcus faecium and Enterococcus faecalis were identified as the species of greatest clinical importance. The aac(6′)-Ie-aph(2″)-Ia and ant(6′)-Ia genes were found to be the most common aminoglycoside-modifying enzyme genes among high-level gentamicin resistance and high-level streptomycin resistance isolates, respectively. Moreover, gelE was the most common virulence gene among high-level aminoglycoside resistance isolates. Compared to Enterococcus faecium, Enterococcus faecalis harbored multiple virulence determinants. The results further indicated no correlation between aminoglycoside-modifying enzyme gene profiles and the distribution of virulence genes among the enterococcal isolates with high-level gentamicin resistance or high-level streptomycin resistance evaluated in our study.

BackgroundInterferon induced transmembrane protein 3 (IFITM3) plays an important role in the tumorigenesis and progression of multiple cancers. This study investigated the expression and function of IFITM3 in human lung adenocarcinoma.MethodsFifty human lung adenocarcinoma tissues were collected. IFITM3 expression was assessed by immunohistochemical staining. The clinicopathologic characteristics of all patients were analyzed.Results IFITM3 was mainly detected in the cytoplasm of advanced cancer tissues and its expression was correlated with tumor malignancy grade. Knockdown of IFITM3 in vitro markedly inhibited the proliferation and invasion of lung adenocarcinoma cells.Conclusion IFITM3 represents a potential therapeutic target for the treatment of lung adenocarcinoma.

Inorganic pyrophosphatase (PPA1) activity is a key determinant of cellular inorganic pyrophosphate levels, and its expression is correlated with growth of several solid tumors. To investigate this relationship, we first examined PPA1 expression in human epithelial ovarian cancer (EOC) samples, and found that PPA1 was overexpressed in tumors from EOC patients. Higher PPA1 levels correlated with advanced grades, stages, and poor survival in EOC patients. Examination of PPA1 function in EOC revealed that silencing PPA1 inhibited EOC migration, epithelial-mesenchymal transition (EMT), and metastasis in vitro and in vivo. In addition, PPA1 may promote the dephosphorylation and translocation of β-catenin. These results demonstrate that silencing PPA1 inhibits EOC metastasis by suppressing the Wnt/β-catenin signaling pathway. Strategies for downregulating PPA1 may have therapeutic potential for the prevention and treatment of EOC.