Survival of Exfoliated Epithelial Cells: A Delicate Balance between Anoikis and Apoptosis
Figure 2
From a physiological point of view, exfoliated epithelial cells resulting from nutritional induction or mild stress are in anoikis by activating a survival mechanism partly using the molecular paths of macroautophagy. Macroautophagy, here referred to as autophagy has been described in amino-acid-free (a) as well as in glucose-free (b) situations. Autophagosome elongation is triggered by lipid modification of LC3 (by phosphatidylethanolamine, PE). The first pathway is linked to growth factors and nutrient-sensing pathways (a), and the second is related to energy-sensing pathway (b). Detachment of extracellular matrix induces both pathways and may activate also the integrated stress response through PERK and eIF2alpha, [16] as such the situation of exfoliated cells is complex and needs more biochemical description to delineate stable molecular tags, useful in assay design, from the labile ones. The experimental starvation of primary or cancerous cells in culture consists in exposing cells to eagle minimum essential medium without serum for few hours. Under these conditions, amino-acid-free situations have been described [37, 38]. Phosphorylation involving Ulk1 in AMPK regulation has been demonstrated [39]. Survivin has also been involved in the inhibition of the conversion of LC3-I to LC3-II form (i.e., acting as an inhibitor of autophagosome formation—[40]) but in cancer cells or stem cells. However, the role of survivin in the turnover of adult cells is still debated [41, 42]. The expression of survivin has been reported in gastric parietal cells both in adult rat and human [38]. Gastric exfoliated epithelial cells of preterm infants do express high amount of survivin suggesting a crucial role of this molecule in the survival of these cells [43, 44]. Glucose starvation occurs at birth [45, 46]. Along with cytokines and drugs, nutritional factors are now considered to be able to alter the balance between cellular survival and death [47].
