Anoikis: To Die or Not to Die?

Epithelial, endothelial and many connective tissue cells are normally attached to the extracellular matrix (ECM). These cells rely on the ECM for structural support, signaling, and regulation of their behavior. When these cells lose this attachment or are in an inappropriate location, they soon die by a mechanism called anoikis (homelessness). Anoikis, is a programmed cell death of apoptotic nature, however, in certain cases it can be overcome and detached cells can survive in the absence of the correct signals from the ECM. This is the case for malignant cells, where anoikis resistance is a prerequisite for invasion and metastasis. Without anoikis resistance (anchorage-independency), tumors would be unable to abandon their normal sites and invade neighboring tissues and metastasize at distant locations. Anoikis is the natural barrier against cancer progression. Therefore, overcoming anoikis is a major step in cellular transformation. Cancer cells have developed many successful strategies to bypass anoikis. The main mechanism, albeit not the only one, involves hyper-activating survival pathways and over-expressing anti-apoptotic molecules. There is a strong and intertwined association between epithelial mesenchymal transition and anoikis resistance that is discussed in depth. A better understanding of anoikis resistance mechanisms has led to the research and development of pharmaceuticals that can counteract them.