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Breast cancer has a marked recurrence and metastatic trait and is one of the most prevalent malignancies affecting women’s health worldwide. Tumor initiation and progression begin after the cell goes from a quiescent to an activated state and requires different mechanisms to act in concert to regulate t a specific set of spectral genes for expression. Cancer stem cells (CSCs) have been proven to initiate and drive tumorigenesis due to their capability of self-renew and differentiate. In addition, CSCs are believed to be capable of causing resistance to anti-tumor drugs, recurrence and metastasis. Therefore, exploring the origin, regulatory mechanisms and ultimate fate decision of CSCs in breast cancer outcomes has far-reaching clinical implications for the development of breast cancer stem cell (BCSC)-targeted therapeutic strategies. In this review, we will highlight the contribution of BCSCs to breast cancer and explore the internal and external factors that regulate the fate of BCSCs.

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Background: Degradation of insulin-like growth factor 1 receptor (IGF-1R) is mediated by internalization and endocytosis, for which ubiquitin-proteasome pathways play as a regulatory system. Cezanne expression is positively associated with IGF-1R expression. High Cezanne expression correlates with poor patient survival in NSCLC, yet the underlying mechanisms are not well defined. Methods: Co-Immunoprecipitation assay was performed to investigate the interactions between Cezanne and IGF-1R. A xenograft model was established to assess the efficacy of Cezanne on cancer progression in vivo. Cezanne overexpressing and Cezanne knockdown NSCLC cell lines were generated using lentiviral vectors. The effects of Cezanne and IGF-1R on cell proliferation of non-small-cell lung cancer were evaluated via Sulforhodamine B assay and colony formation assays. Results: Here, through co-Immunoprecipitation assay, we find Cezanne interacts with IGF-1R in tumor cells. Depletion of Cezanne promotes the ubiquitination and degradation of IGF-1R. Congruently, Cezanne regulates the protein level of IGF-1R and downstream AKT signaling pathway. Cezanne promotes proliferation of tumor cells in vitro and in vivo. In line with the change of IGF-1R downstream signaling pathway, IGF-1-induced growth signals recover cell proliferation of tumor cells with Cezanne knockdown. Conclusion: Mechanistically, Cezanne directly targets IGF-1R by deubiquitination and stabilization. This leads to AKT activation, which bolsters tumor cell growth in vitro and in vivo. These findings reveal Cezanne as a regulator of tumor cell proliferation via IGF-1R signaling pathway and a potential target for NSCLC therapy.

Previous studies suggested that diabetes mellitus (DM) was associated with risk and mortality of cancer, but studies investigating the correlation between DM and lung cancer prognosis remain controversial. Herein, a meta-analysis was performed to derive a more precise estimate of the prognostic role of DM in lung cancer. Medline and Embase were searched for eligible articles from inception to October 25, 2015. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) was calculated to evaluate the correlation between DM and lung cancer prognosis. Subgroup meta-analysis was performed based on the histology and the treatment methods. A total of 20 cohort studies from 12 articles were included in the meta-analysis. Also, 16 studies investigated the overall survival (OS) and 4 studies investigated the progression-free survival (PFS). DM was significantly associated with the inferior OS of lung cancer with the pooled HR 1.28 (95% CI: 1.10–1.49, P = 0.001). The association was prominent in the nonsmall cell lung cancer (NSCLC) subgroup (HR 1.35, 95%CI: 1.14–1.60, P = 0.002), whereas the association was not significant in the small cell lung cancer (SCLC) subgroup (HR 1.33, 95% CI: 0.87–2.03, P = 0.18). When NSCLC patients were further stratified by treatment methods, DM had more influence on the surgically treated subgroup than the nonsurgically treated subgroup. There was no obvious evidence for publication bias by Begg's and Egger's test. The results of this meta-analysis exhibit an association of DM with inferior prognosis amongst lung cancer patients, especially the surgically treated NSCLC patients. Given the small number of studies included in this meta-analysis, the present conclusion should be consolidated with more high-quality prospective cohort studies or randomized controlled trials.