Hypoxia is a common feature of most tumors and is a product of rapid cell growth and poor vascularization1. When oxygen availability is low in the tumor environment, the hypoxia inducing transcription factors (HIFs) regulate a variety of signaling programs that can affect the balance between tumor cell apoptosis2 and autophagy3. In normoxia, HIFs are bound by the von Hippel-Lindau protein (VHL) in the cytosol where it is degraded by the proteasome, however, under hypoxia HIFs are translocated to the nucleus where they activate survival signals.
Altered cellular membrane integrity is one of the earliest signs of apoptosis.1,2 One key change during this event is the movement of phosphatidylserine (PS) from the inner leaflet of the cell membrane towards the cell surface.
Different types of cell death have classically been identified by discrete morphological changes. The hallmarks of apoptosis include cell shrinkage, nuclear fragmentation and membrane blebbing whereas necroptosis is characterized by cell swelling and plasma membrane breakdown. While these two forms of cell death are clearly distinct, substantial crosstalk occurs between them. Accordingly, it is becoming increasingly important to understand how these processes differ and to understand ways to differentiate them in cellular populations.
Have you ever wondered why cells in the same population respond differently to an apoptotic stimulus? Apoptosis, a form of programmed cell death, is vital for the removal of unwanted or damaged cells. As with most cellular processes, too much or too little activation can be detrimental and lead to various diseases including autoimmune disorders and cancer.
Apoptosis is a form of programmed cell death which is mediated by cysteine proteases called caspases. It is an essential phenomenon in the maintenance of homeostasis and growth of tissues, and it also plays a critical role in immune response. The cytomorphological alterations and the key features of apoptosis are listed below:
YAP1 (Yes-associated protein 1) is a transcriptional co-activator which acts as a major effector of Hippo signaling pathway that regulates organ size/ tissue homeostasis and cell proliferation, and is an established oncogene (1). Hippo signaling activation results in the phosphorylation mediated inactivation of YAP1, and restriction of YAP1’s transcriptional activity is the principal mechanism of growth and tumor suppression by Hippo pathway.
