Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumourigenesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and cell–cell adhesion, including the cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo, and strongly repressed promotor activities in reporter assays. ZEB1 downregulation in undifferentiated cancer cells by RNA interference was sufficient to upregulate expression of these cell polarity genes on the RNA and protein level, to re-establish epithelial features and to impair cell motility in vitro. In human colorectal cancer, ZEB1 expression was limited to the tumour–host interface and was accompanied by loss of intercellular adhesion and tumour cell invasion. In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer cell dedifferentiation. Our data show that ZEB1 represents a key player in pathologic EMTs associated with tumour progression.

Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program “epithelial-mesenchymal transition” (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression. [Cancer Res 2008;68(2):537–44]

In recent years there has been tremendous interest in both the basic biology and applications of extracellular vesicles (EVs) in translational cancer research. This includes a better understanding of their biogenesis and mechanisms of selective cargo packaging, their precise roles in horizontal communication, and their application as non-invasive biomarkers. The rapid advances in next-generation omics technologies are the driving forces for these discoveries. In this review, the authors focus on recent results of EV research in ovarian cancer. A deeper understanding of ovarian cancer-derived EVs, the types of cargo molecules and their biological roles in cancer growth, metastases and drug resistance, could have significant impact on the discovery of novel biomarkers and innovative therapeutics. Insights into the role of EVs in immune regulation could lead to novel approaches built on EV-based immunotherapy.

Breast cancer is the leading cause of morbidity and mortality globally but has an even more significant impact in developing countries. Pakistan has the highest prevalence among Asian countries. A general lack of public awareness regarding the disease often results in late diagnosis and poor treatment outcomes. The literacy rate of the Southern Punjab (Pakistan) is low compared to its Northern part. It is therefore vital that university students and especially medical students develop a sound knowledge about the disease so that they can spread awareness to others who may be less educated. This study therefore considers current knowledge and understanding about the early signs of breast cancer amongst a study group of medical and non-medical university students of the Southern Punjab, Pakistan. A cross-sectional descriptive analysis of the university students was carried out using a self-administered questionnaire to assess their awareness of breast cancer from March to May 2014. A total of 566 students participated in this study, out of which 326 were non-medical and 240 were from a medical discipline. Statistical analysis was carried out using Graph Pad Prism Version 5 with a significance level set at p<0.05. The mean age of the non medical and medical participants was 23 (SD 2.1) and 22 (SD 1.3) years, respectively. Less than 35% students were aware of the early warning signs of the breast cancer development. Knowledge of medical students about risk factors was significantly better than the non medical ones, but on the whole was insufficient. Our study indicated that knowledge regarding breast cancer was generally insufficient amongst the majority of the university students (75% non-medical and 55% medical) of Southern Punjab, Pakistan. This study highlights the need to formulate an awareness campaign and to organize conferences to promote breast cancer awareness among students in this region.