Role of Autophagy in Cancer Cell Response to Nucleolar and Endoplasmic Reticulum Stress

Abstract

Eukaryotic cells are exposed to many internal and external stimuli that affect their fate. In particular, the exposure to some of these stimuli induces stress triggering a variety of stress responses aimed to re-establish cellular homeostasis. It is now established that the deregulation of stress response pathways plays a central role in cancer initiation and progression, allowing the adaptation of cells to an altered state in the new environment. Autophagy is a tightly regulated pathway which exerts “housekeeping” role in physiological processes. Recently, a growing amount of evidence highlighted the crucial role of autophagy in the regulation of integrated stress responses, including nucleolar and endoplasmic reticulum. In this review, we attempt to afford an overview of the complex role of nucleolar and endoplasmic reticulum stress-response mechanisms in the regulation of autophagy in cancer and cancer treatment.

S-Adenosyl-l-Methionine Overcomes uL3-Mediated Drug Resistance in p53 Deleted Colon Cancer Cells

“…Autophagy plays a role as a pro-survival mechanism for drug resistance [ 36 ]. We have recently demonstrated that the chemoresistance observed in uL3∆HCT 116 p53−/− cells might depend on the higher autophagic flux displayed by this cell population [ 11 ].…”

“…However, in established tumors, it may act as a pro-survival pathway during stress conditions like nutrient deprivation, hypoxia, and cancer therapeutic treatment. Moreover, the inhibition of autophagy has been shown to prevent resistance of cancer cells to chemotherapy [ 36 ]. Recently, we have shown that resistance to drugs caused by uL3 depletion in p53-deleted colon cancer cells was due to autophagy induction [ 11 ].…”

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

“…eL19 (L19) also activates the UPR, sensitizing breast cancer cells to ER stress-induced cell death, but the mechanism by which eL19 exerts this effect has not been fully elucidated [ 79 ]. More recently, transcriptomic RNA seq analysis of colon cancer cells devoid of p53 and stably silenced of uL3 has evidenced the activation of the UPR pathway, providing evidence of uL3 involvement in the regulation of this process [ 80 , 81 ].…”

“…The UPR and autophagy are interconnected and, recently, a link between the altered expression of some CRPs and autophagy modulation has emerged. Several stresses induced by mutations or deficiency of some CRPs may lead to autophagy induction in different cell types [ 81 ]. To date, in breast and ovarian cancer cell lines, the depletion of RPs such as uL10, RPLP1 and RPLP2 causes an increase in autophagic occurrence [ 82 ], whereas RPS27L silencing causes the blockage of this process via the mammalian target of rapamycin complex 1 (mTORC1) inactivation [ 83 ].…”

“…Recently, our research group has highlighted the role of uL3 as a negative regulator of autophagy in colon cancer. Analysis of the autophagic flux has demonstrated that uL3 overexpression markedly suppresses autophagic flux, which is associated with the decreased expression of protein components of autophagy, initiating the ULK complex [ 80 , 81 ]. Accordingly, in uL3-deleted colon cancer cells, the autophagic flux was most markedly increased.…”