Autophagy and EMT in cancer and metastasis: Who controls whom?

Metastasis consists of hallmark events, including Epithelial-Mesenchymal Transition (EMT), angiogenesis, initiation of inflammatory tumor microenvironment, and malfunctions in apoptosis. Autophagy is known to play a pivotal role in the metastatic process. Autophagy has pulled researchers towards it in recent times because of its dual role in the maintenance of cancer cells. Evidence states that cells undergoing EMT need autophagy in order to survive during migration and dissemination. Additionally, it orchestrates EMT markers in certain cancers. On the other side of the coin, autophagy plays an oncosuppressive role in impeding early metastasis. This review aims to project the interrelationship between autophagy and EMT. Targeting EMT via autophagy as a useful strategy is discussed in this review. Furthermore, for the first time, we have covered the possible reciprocating roles of EMT and autophagy and its consequences in cancer metastasis.     

Autophagy and apoptosis: what is the connection?

The therapeutic potential of autophagy for the treatment cancer and other diseases is beset by paradoxes stemming from the complexity of the interactions between the apoptotic and autophagic machinery. The simplest question of how autophagy acts as both a protector and executioner of cell death remains the subject of substantial controversy. Elucidating the molecular interactions between the processes will help us understand how autophagy can modulate cell death, whether autophagy is truly a cell death mechanism, and how these functions are regulated. We suggest that, despite many connections between autophagy and apoptosis, a strong causal relationship wherein one process controls the other, has not been demonstrated adequately. Knowing when and how to modulate autophagy therapeutically depends on understanding these connections.     

Intracellular Quality Control by Autophagy: How Does Autophagy Prevent Neurodegeneration?

Autophagy is an intracellular bulk degradation process, through which a portion of cytoplasm is delivered to lysosomes to be degraded. In many organisms, the primary role of autophagy is adaptation to starvation. However, we have found that autophagy is also important for intracellular protein quality control. Atg5^-/- mice die shortly after birth due, at least in part, to nutrient deficiency. These mice also exhibit an intracellular accumulation of protein aggregates in neurons and hepatocytes. We now report the generation of neural cell-specific Atg5-deficient mice. Atg5^flox/flox;Nestin-Cre mice show progressive deficits in motor function and degeneration of some neural cells. In autophagy-deficient cells, diffuse accumulation of abnormal proteins occurs, followed by the generation of aggregates and inclusions. This study emphasizes the point that basal autophagy is important even in individuals who do not express neurodegenerative disease-associated mutant proteins. Furthermore, the primary targets of autophagy are diffuse cytosolic proteins, not protein aggregates themselves.     

Who owns the data?

About ten years ago, a group of scientists began to argue that it was unfair to ask other scientists to pay to read the results of research that had been publicly funded.     

Autophagy across the eukaryotes: Is S. cerevisiae the odd one out?

Autophagy is conserved throughout the eukaryotes and for many years, work in Saccharomyces cerevisiae has been at the forefront of autophagy research. However as our knowledge of the autophagic machinery has increased, differences between S. cerevisiae and mammalian cells have become apparent. Recent work in other organisms, such as the amoeba Dictyostelium discoideum, indicate an autophagic pathway much more similar to mammalian cells than S. cerevisiae, despite its earlier evolutionary divergence. S. cerevisiae therefore appear to have significantly specialized, and the autophagic pathway in mammals is much more ancient than previously appreciated, which has implications for how we interpret data from organisms throughout the eukaryotic tree.     

Autophagy in endometriosis: Friend or foe?

Endometriosis is a chronic, estrogen-dependent disease and characterized by the implantation of endometrial glands and stroma deep and haphazardly into the outside the uterine cavity. It affects an estimated 10% of the female population of reproductive age and results in obvious reduction in health-related quality of life. Unfortunately, there is no a consistent theory for the etiology of endometriosis. Furthermore, the endometriosis is hard to diagnose in early stage and the treatment methods are limited. Importantly, emerging evidence has investigated that there is a close relationship between endometriosis and autophagy. However, autophagy is a friend or foe in endometriosis is puzzling, the precise mechanism underlying autophagy in endometriosis has not been fully elucidated yet. Here, we provide an integrated view on the acquired findings of the connections between endometriosis and autophagy. We also discuss which may contribute to the abnormal level of autophagy in endometriosis.     

Who speaks for the dispossessed?

This commentary articulates three perspectives on race in America: economic determinism, institutionalism and a field-theoretic approach. It argues that William Julius Wilson's masterwork, The Declining Significance of Race, was informed by the first and anticipated the latter two. Wilson's most profound and enduring legacy is his unwavering concern for the dispossessed.     

Who cares for the protons?

It is tempting to use standard protonation states for the analysis of protein-ligand interactions. Two different pK(a) calculation methods, PROPKA (protein pK(a)) and MCCE (multi conformation continuum electrostatics), were applied to challenge this convenient behavior. As data basis, we selected five recently approved drugs for which structural information of the protein-drug complex is available. We analyzed the pK(a) calculations in terms of a measure termed BIPS (binary protonation states) recently introduced by us. Both methods agree in detecting the majority of the sites with atypical BIPS values. However, when using only one method, some of the atypcial BIPS value would have been missed. Therefore, we recommend using both methods to set such an interpretation on a solid basis.     

Who owns the Brazilian carbon?

Brazil is one of the major contributors to land‐use change emissions, mostly driven by agricultural expansion for food, feed, and bioenergy feedstock. Policies to avoid deforestation related to private commitments, economic incentives, and other support schemes are expected to improve the effectiveness of current command and control mechanisms increasingly. However, until recently, land tenure was unknown for much of the Brazilian territory, which has undermined the governance of native vegetation and challenged support and incentive mechanisms for avoiding deforestation. We assess the total extent of public governance mechanisms protecting aboveground carbon (AGC) stocks. We constructed a land tenure dataset for the entire nation and modeled the effects and uncertainties of major land‐use acts on protecting AGC stocks. Roughly 70% of the AGC stock in Brazil is estimated to be under legal protection, and an additional 20% is expected to be protected after areas in the Amazon with currently undesignated land undergo a tenure regularization. About 30% of the AGC stock is on private land, of which roughly two‐thirds are protected. The Cerrado, Amazon, and Caatinga biomes hold about 40%, 30%, and 20% of the unprotected AGC, respectively. Effective conservation of protected and unprotected carbon will depend on successful implementation of the Forest Act, and regularization of land tenure in the Amazon. Policy development that prioritizes unprotected AGC stocks is warranted to promote conservation of native vegetation beyond the legal requirements. However, different biomes and land tenure structures may require different policy settings considering local and regional specifics. Finally, the fate of current AGC stocks relies upon effective implementation of command and control mechanisms, considering that unprotected AGC in native vegetation on private land only accounts for 6.5% of the total AGC stock.