Polarity in embryogenesis and yin and yang theory

The main molecular events are depicted in Figure 1.Дў. The cellular processes of EMT are coordinated by several key transcription factors (e.g., TWIST, SNAI1, SNAI2, ZEB 1/2) that act in unison with several epigenetic mechanisms and post-translational protein modifications to arrange the cellular alterations. In PCa, for instance, loss of E-cadherin expression and overexpression of N-cadherin correlate with tumor grade and recurrence after surgery, providing a clinically significant link of EMT to aggressive clinical behavior in advanced disease. In cancer progression, this is connected with poor clinical outcome and therapy resistance in several cancer types. EMT is identified by a loss of epithelial markers such as cytokeratins and E-cadherin, followed by a concurrent increase in mesenchymal markers such as N-cadherin and vimentin. During EMT, epithelial cells lose their junctions and apicalвЂ“basal polarity, restructure their cytoskeleton, undergo changes in the signaling programs that specify cell shape, and reprogram gene expression this enhances the motility of individual cells and empowers the progression of a more invasive phenotype. EpithelialвЂ“mesenchymal transition (EMT) is a molecular cellular program essential for development, and the relevant processes are reactivated during wound healing, fibrosis, and cancer progression. Recently, ample evidence of epithelialвЂ“mesenchymal plasticity playing a role in both PCa metastatic progression and treatment resistance has been provided in several reports. Thus, understanding the cellular and molecular mechanisms underlying the process of metastatic dissemination of PCa remains a challenge for better management of PCa. The critical problem in the available pharmaceutical therapeutic approach of PCa is that PCa unavoidably develops resistance to androgen deprivation therapy (ADT) at some stage and progresses to castration-resistant PCa (CRPC), which is characterized by invasiveness and metastatic spread of CRPC cells this phenomenon still represents the major cause of PCa-related death. This excessive heterogeneity and plasticity which characterize prostate tumors underline the regulatory phenotypic changes in individual cells that contribute to metastasis and therapeutic resistance.

It is well known that PCa is a multifocal disease with a heterogeneous cell population. The highest mortality rates are expected in Africa (+124.4%) and Asia (116.7%), while the lowest incidence is expected to be registered in Europe (+58.3%). It is estimated that mortality will double from 2018 to 2040, reaching 379,005 deaths worldwide. However, this is also true for men generally the incidence of PCa in young men is rising, and their younger age poses a higher risk for metastatic disease and eventually a higher mortality. For African American men, the incidence rates are higher when compared to White men alarmingly, they also have the highest chance of being diagnosed at a younger age (<40 years). As a general rule, both incidence and mortality of PCa correlate with advancing age, with the average age at the time of diagnosis being 66 years. Prostate cancer (PCa) is the second most frequently diagnosed male malignancy and the second leading cause of cancer mortality in men.

In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. These changes include enhanced motility and loss of cellвЂ“cell adhesion that form a more aggressive cellular phenotype. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. EpithelialвЂ“mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges.

Polarity in embryogenesis and yin and yang theory