The metastatic process in breast cancer is related to the expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1 and TWIST1. EMT-TFs and nuclear factor-κB (NF-κB) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-κB in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-κB/p65 activity by reducing its transcript and protein levels (through siRNA-strategy and dehydroxymethylepoxyquinomicin [DHMEQ] treatment) in the aggressive MDA-MB-231 and HCC-1954 cell lines resulted in decreased invasiveness and migration, a downregulation of SLUG, SIP1, TWIST1, MMP11 and N-cadherin transcripts and an upregulation of E-cadherin transcripts. No significant changes were observed in the less aggressive cell line MCF-7. Bioinformatics tools identified several NF-κB binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-κB/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-κB directly regulates the transcription of EMT-TF genes in breast cancer. Our findings may contribute to a greater understanding of the metastatic process of this neoplasia and highlight NF-κB as a potential target for breast cancer treatment.

Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies. In addition to the direct effects of NF-κB in cancer cells, it might also impact immune cells that can both promote or prevent tumor development. Currently, with the rise of cancer immunotherapy, the link among immune cells, inflammation, and cancer is a major focus, and NF-κB could be an important regulator for the success of these therapies. This review discusses the contrasting roles of NF-κB as a regulator of pro- and antitumor processes and its potential as a therapeutic target.

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Breast cancer is the leading cause of cancer-associated death among women worldwide. Its high mortality rate is related to resistance towards chemotherapies, which is one of the major challenges of breast cancer research. In this study, we used label-free mass spectrometry- (MS-) based proteomics to investigate the differences between circulating proteins in the plasma of patients with chemoresponsive and chemoresistant luminal A breast cancer. MS analysis revealed 205 differentially expressed proteins. Furthermore, we used in silico tools to build protein-protein interaction networks. Most of the upregulated proteins in the chemoresistant group were closely related and tightly linked. The predominant networks were related to oxidative stress, the inflammatory response, and the complement cascade. Through this analysis, we identified inflammation and oxidative stress as central processes of breast cancer chemoresistance. Furthermore, we confirmed our hypothesis by evaluating oxidative stress and performing cytokine profiling in our cohort. The connections among oxidative stress, inflammation, and the complement system described in our study seem to indicate a pivotal axis in breast cancer chemoresistance. Hence, these findings will have significant clinical implications for improving therapies to bypass breast cancer chemoresistance in the future.

Laryngeal cancer is a significant disease worldwide, which presents an increasing incidence. Two contrasting ideas of the immune system role during cancer development are accepted: (1) it fights tumor cells, and (2) it aids tumor progression. Thus, there is no clear understanding about the immune response in laryngeal cancer. Furthermore, since tobacco is the main cause of laryngeal cancer and it contains various carcinogenic components, including metallic elements, these may play a role on cancer development. Plasmas of patients with laryngeal cancer and of healthy smokers were evaluated by 2D gel electrophoresis and mass spectrometry. Proteins were detected on every gel around pH 4.0-10.0 from molecular mass of 10-60 kDa. Few differences were found among cancer and control patients. However, three spots gathered between pI 7.3 and 7.6 with different molecular masses appeared exclusively in cancer profiles. From ten spots identified, six correspond to immune system components, including the three differential ones. The latter were observed only in cancer patients. The presence of several trace elements in the identified proteins was determined by inductively coupled plasma mass spectrometry, where chromium was increased in all proteins analyzed from patients with cancer. This study reinforces the importance of the immune response as target in the understanding and treatment of laryngeal cancer and the possibility that chromium is important in the carcinogenic progress.

Background/Aim: Although the knowledge regarding adrenocortical carcinomas (ACC) tumorigenesis has significantly improved during the last decade, it still remains to be completely determined. Epithelialmesenchymal transition (EMT) is a well described transcription factor induced process, postulated as an essential step toward cancer progression and metastasis development. In this context, Twist1 has been described as the EMT master-regulator. The aim of this study was to assess the association among Twist1, fibronectin, vimentin and Ecadherin gene expression in adrenocortical tumor samples. Materials and Methods: Twist1, fibronectin, vimentin and Ecadherin gene expression in 18 adrenal adenomas, 18 ACC, and 24 childhood onset adrenocortical tumors were assessed in formalin-fixed paraffin-embedded tissues. The fold expression was calculated according to the 2 ΔCt method. Results: A significant correlation between mRNA levels of Twist1, fibronectin and vimentin was evident. Although their expression was inversely proportional, no association was observed between Twist1 and E-cadherin expression. Conclusion: The expression of Twist1, the major regulator of EMT, is directly correlated to the expression of mesenchymal markers fibronectin and vimentin in ACC samples.

Breast cancer treatment has advanced enormously in the last decade. Most of this is due to advances reached in the knowledge regarding tumor biology, mainly in the field of diagnosis and treatment. This review brings information about how the genomics-based information contributed to advances in breast cancer diagnosis and prognosis perspective, as well as presents how tumor biology discoveries fostered the main therapeutic approaches available to treat such patients, based on a personalized point of view.

Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.