Divergent Roles of Mitochondria Dynamics in Pancreatic Ductal Adenocarcinoma.

Abstract

Simple SummaryPancreatic ductal adenocarcinoma is one of the most lethal neoplasia due to the lack of early diagnostic markers and effective therapies. The study of metabolic alterations of PDAC is of crucial importance since it would open the way to the discovery of new potential therapies. Mitochondria represent key organelles that regulate energy metabolism, and they remodel their structure by undergoing modifications by fusing with other mitochondria or dividing to generate smaller ones. The alterations of mitochondria arrangement may influence the metabolism of PDAC cells, thus supporting the proliferative needs of cancer. Shedding light on this topic regarding cancer and, more specifically, PDAC may help identify new potential strategies that hit cancer cells at their “core,” i.e., mitochondria.Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors; it is often diagnosed at an advanced stage and is hardly treatable. These issues are strictly linked to the absence of early diagnostic markers and the low efficacy of treatment approaches. Recently, the study of the metabolic alterations in cancer cells has opened the way to important findings that can be exploited to generate new potential therapies. Within this scenario, mitochondria represent important organelles within which many essential functions are necessary for cell survival, including some key reactions involved in energy metabolism. These organelles remodel their shape by dividing or fusing themselves in response to cellular needs or stimuli. Interestingly, many authors have shown that mitochondrial dynamic equilibrium is altered in many different tumor types. However, up to now, it is not clear whether PDAC cells preferentially take advantage of fusion or fission processes since some studies reported a wide range of different results. This review described the role of both mitochondria arrangement processes, i.e., fusion and fission events, in PDAC, showing that a preference for mitochondria fragmentation could sustain tumor needs. In addition, we also highlight the importance of considering the metabolic arrangement and mitochondria assessment of cancer stem cells, which represent the most aggressive tumor cell type that has been shown to have distinctive metabolic features to that of differentiated tumor cells.