It is likely that the genes which act to block the apoptotic process are responding as a cellular survival mechanism, although some may be directly activated via the TNFα signalling pathway.
Although it has been traditionally thought that autophagy was a catabolic process involving lysosomal degradation in response to lack of nutrients, autophagy is emerging as a cellular survival mechanism against a variety of stressors.
This may be related to activation of the phosphatidylinositol 3-kinase (PI3K), a growth factor and TNFα -activated lipid kinase, which is associated with a cellular survival response.
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis.
Autophagy is a fundamental cellular survival response during nutrient starvation, permitting cells to maintain nutrient and energy homeostasis when external food supply is limited (Levine and Klionsky, 2004).
We conclude that besides a neurotrophic factor, Manf is an important cellular survival factor needed to overcome the UPR especially in tissues with high secretory function.
Importantly, it can be predicted that long-term fragmentation of the ER is likely to be incompatible with cellular survival.
In a genome wide approach, genes related to mitochondrial proteins were found to be crucial for cellular survival.
Activation of AMPK inhibits the mammalian target of rapamycin (mTOR), a protein known to be a driver of cellular survival and proliferation in human cancer and one that is activated by IGF-1 [ 27].
Since housekeeping genes are required for cellular survival, it is assumed that they are stably expressed and are often used without validating their suitability.
