Jab1/Csn5 Signaling in Breast Cancer

c-Jun activation domain-binding protein1 (Jab1), also known as a monomer or the fifth component of the constitutive photomorphogenesis 9 signalosome (Csn5) complex, regulates cell proliferation, cell-cycle progression, and apoptosis and affects a series of pathways. Jab1/Csn5 also promotes cell transformation and tumorigenesis, and its overexpression in many tumor types suggests it is involved in cancer progression and closely associated with poor cancer prognosis. Jab1/Csn5 dysregulation contributes to oncogenesis by deactivating several tumor suppressors. Increasing evidence of the role of Jab1/Csn5 overexpression in breast and other cancers has spurred interest in Jab1/Csn5 inhibitors for cancer therapy. In this chapter, we summarize the evidence demonstrating the importance of Jab1/Csn5 expression in breast and other cancers and review recent advances in dissecting the Jab1/Csn5 signaling pathway along with its potential as a therapeutic target for cancer

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Background/Aims: MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer. Methods: In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo. Results: In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis. Conclusion: These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients

Clinical Significance of Elevated S100A8 Expression in Breast Cancer Patients

Breast cancer is the leading cause of female cancer-related death; however, novel biomarkers for predicting cancer recurrence still need to be explored. Aberrant expression of S100A8 has been reported to be related to tumor progression in various cancer types. This study aims to evaluate the clinical significance of S100A8 expression in breast cancer patients. In this study, data from 140 breast cancer patients were retrospectively collected to examine the association between S100A8 expression and clinical prognosis. Increased S100A8 expression was detected in breast cancer patients with relapse. The patients with increased S100A8 levels had significantly shorter disease-free survival (DFS) and overall survival (OS). In a multivariate survival analysis, a high histological grade and an elevated S100A8 level were independent factors associated with poor DFS and OS. Moreover, S100A8 expression was correlated with clinical subtype in breast cancer patients. The results showed that ER-negative and triple-negative breast cancer (TNBC) patients had significantly higher expression of S100A8 than patients with other subtypes. In conclusion, this study identified S100A8 as a potential biomarker for relapse in breast cancer patients

Association Between c-Myc and Colorectal Cancer Prognosis: A Meta-Analysis

Background: There is debate as to whether c-Myc predicts prognosis in colorectal cancer (CRC). In this study, we aimed to review the association between c-Myc and CRC prognosis.Methods: Pertinent studies were identified by searching electronic databases and carefully reviewing the reference lists of pertinent studies until March 2016. The summary hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated to study the association between c-Myc and CRC prognosis.Results: Eight cohort studies (including seven studies about overall survival [OS] and one study about disease free survival [DFS]) were included. The pooled HR of OS was 1.13 (95% CI: 0.66–1.95). In subgroup analysis, no significant association between c-Myc and CRC prognosis was found in the studies either from Western countries (HR: 0.87, 95% CI: 0.68–1.10) or Asian countries (HR: 1.89, 95% CI: 0.62–5.77). HRs were 0.86 (95% CI: 0.38–1.94) and 1.57 (95% CI: 0.73–3.39) for the studies using univariate analysis and multivariate analysis, respectively. HR from the studies that examined DNA level was significantly different (HR: 2.05, 95% CI: 1.22–3.46); while that about RNA level or protein level was not significantly different.Conclusion: c-Myc was not associated with CRC prognosis in this meta-analysis. However, the conclusion is preliminary and should be examined in future studies

Jab1/COPS5 as a Novel Biomarker for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Human Cancer

C-Jun activation domain-binding protein-1 (Jab1) involves in controlling cellular proliferation, cell cycle, apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage response (DDR). Jab1/COPS5 dysregulation contributes to oncogenesis by deactivating several tumor suppressors and activating oncogenes. Jab1 overexpression was found in many tumor types, illuminating its important role in cancer initiation, progression, and prognosis. Jab1/COPS5 has spurred a strong research interest in developing inhibitors of oncogenes/oncoproteins for cancer therapy. In this paper, we present evidences demonstrating the importance of Jab1/COPS5 overexpression in several cancer types and recent advances in dissecting the Jab1/COPS5 upstream and downstream signaling pathways. By conducting ingenuity pathway analysis (IPA) based on the Ingenuity Knowledge Base, we investigated signaling network that interacts with Jab1/COPS5. The data confirmed the important role of Jab1/COPS5 in tumorigenesis, demonstrating the potential of Jab1/COPS5 to be used as a biomarker for cancer patients, and further support that Jab1/COPS5 may serve as a potential therapeutic target in different cancers

Functional crosstalk and regulation of natural killer cells in tumor microenvironment: Significance and potential therapeutic strategies

Natural killer (NK) cells eliminate a large variety of tumor cells and abnormal cells. However, NK cells in the tumor microenvironment (TME) are often functionally depleted. A few subsets of NK cells even promote tumor growth. This study reviewed the biological properties of NK cells, the dynamic phenotypic changes of NK cells in the TME, and the communication between NK cells and other immune and nonimmune cells

P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients.

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC

Correction: Stat3 inhibitor stattic exhibits potent antitumor activity and induces chemo- and radio-sensitivity in nasopharyngeal carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0054565.]