Contribution of ER Stress to Immunogenic Cancer Cell Death

2012 ◽  
pp. 413-428 ◽  
Author(s):  
Abhishek D. Garg ◽  
Dmitri V. Krysko ◽  
Jakub Golab ◽  
Peter Vandenabeele ◽  
Patrizia Agostinis
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Cancer Cell Death

γ-Tocotrienol-induced endoplasmic reticulum stress and autophagy act concurrently to promote breast cancer cell death

2015 ◽  
Vol 93 (4) ◽  
pp. 306-320 ◽  
Author(s):  
Roshan V. Tiwari ◽  
Parash Parajuli ◽  
Paul W. Sylvester
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Human Breast Cancer ◽  
Beclin 1 ◽  
Time Dependent ◽  
Human Breast ◽  
Cancer Cell Death

The anticancer effects of γ-tocotrienol are associated with the induction of autophagy and endoplasmic reticulum (ER) stress-mediated apoptosis, but a direct relationship between these events has not been established. Treatment with 40 μmol/L of γ-tocotrienol caused a time-dependent decrease in cancer cell viability that corresponds to a concurrent increase in autophagic and endoplasmic reticulum (ER) stress markers in MCF-7 and MDA-MB-231 human breast cancer cells. γ-Tocotrienol treatment was found to cause a time-dependent increase in early phase (Beclin-1, LC3B-II) and late phase (LAMP-1 and cathepsin-D) autophagy markers, and pretreatment with autophagy inhibitors Beclin-1 siRNA, 3-MA or Baf1 blocked these effects. Furthermore, blockage of γ-tocotrienol-induced autophagy with Beclin-1 siRNA, 3-MA, or Baf1 induced a modest, but significant, reduction in γ-tocotrienol-induced cytotoxicity. γ-Tocotrienol treatment was also found to cause a decrease in mitogenic Erk1/2 signaling, an increase in stress-dependent p38 and JNK1/2 signaling, as well as an increase in ER stress apoptotic markers, including phospho-PERK, phospho-eIF2α, Bip, IRE1α, ATF-4, CHOP, and TRB3. In summary, these finding demonstrate that γ-tocotrienol-induced ER stress and autophagy occur concurrently, and together act to promote human breast cancer cell death.

Abstract 1234: The anticancer drug ABTL0812 induces cancer cell death by impairing Akt/mTORC1 axis and inducing ER stress-mediated cytotoxic autophagy

2020 ◽  
Author(s):  
Pau Muñoz-Guardiola ◽  
Josefina Casas ◽  
Elisabet Megías-Roda ◽  
Hector Perez-Montoyo ◽  
Sonia Solé-Sánchez ◽  
...  
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Cancer Cell Death

Upregulation of miR-133a-3p enhances Bufothionine-induced gastric cancer cell death by modulating IGF1R/PI3K/Akt signal pathway mediated ER stress

Life Sciences ◽  
2020 ◽  
Vol 259 ◽  
pp. 118180
Author(s):  
Zhi-Hao Hu ◽  
Guo-Jun Wang ◽  
Rui-Xin Li ◽  
Tian-Yu Zhu ◽  
Zhuo-Yin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Signal Pathway ◽  
Cancer Cell Death

scholarly journals ER Stress Signaling and its Role in Cancer Cell Death

2021 ◽  
Vol 8 (S1-Feb) ◽  
pp. 81-86
Author(s):  
Kavitha C V ◽  
Poornima S K
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Unfolded Protein ◽  
Cancer Cell Death ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Cellular Dysfunction

The endoplasmic-reticulum (ER) stress response represents a cellular process that is provoked by a number of circumstances that disturb folding of proteins in the ER. An evolutionarily conserved adaptive mechanismhas been developed by Eukaryotic cells, termed the unfolded protein response (UPR) to clear the unfolded proteins and restore ER homeostasis. The cellular functions deteriorate, in the conditions when ER stress cannot be reversed and this sometime lead to cell death.The poor vascularization, low oxygen supply, nutrient deprivation, and acidic pH in the tumor microenvironment stimulate the ER stress. UPR has been shown to exert a significantcytoprotective part in speedily growing cancers as it helps folding of newly synthesized proteins required for the growth of the tumor.Accumulating evidence showed that ER stress-induced cellular dysfunction and cell death are the major contributors to many diseases and making the modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Herein, we will briefly summarize gesticulating cascade activated upon ER stress and its role in cancer cell death.

scholarly journals ERK5 Inhibition Induces Autophagy-Mediated Cancer Cell Death by Activating ER Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Andrés Gámez-García ◽  
Idoia Bolinaga-Ayala ◽  
Guillermo Yoldi ◽  
Sergio Espinosa-Gil ◽  
Nora Diéguez-Martínez ◽  
...  
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cellular Response ◽  
Negative Regulator ◽  
Autophagic Flux ◽  
Chemical Chaperone ◽  
Cancer Cell Death ◽  
Major Player

Autophagy is a highly conserved intracellular process that preserves cellular homeostasis by mediating the lysosomal degradation of virtually any component of the cytoplasm. Autophagy is a key instrument of cellular response to several stresses, including endoplasmic reticulum (ER) stress. Cancer cells have developed high dependency on autophagy to overcome the hostile tumor microenvironment. Thus, pharmacological activation or inhibition of autophagy is emerging as a novel antitumor strategy. ERK5 is a novel member of the MAP kinase family that is activated in response to growth factors and different forms of stress. Recent work has pointed ERK5 as a major player controlling cancer cell proliferation and survival. Therefore small-molecule inhibitors of ERK5 have shown promising therapeutic potential in different cancer models. Here, we report for the first time ERK5 as a negative regulator of autophagy. Thus, ERK5 inhibition or silencing induced autophagy in a panel of human cancer cell lines with different mutation patterns. As reported previously, ERK5 inhibitors (ERK5i) induced apoptotic cancer cell death. Importantly, we found that autophagy mediates the cytotoxic effect of ERK5i, since ATG5ˉ/ˉ autophagy-deficient cells viability was not affected by these compounds. Mechanistically, ERK5i stimulated autophagic flux independently of the canonical regulators AMPK or mTORC1. Moreover, ERK5 inhibition resulted in ER stress and activation of the Unfolded Protein Response (UPR) pathways. Specifically, ERK5i induced expression of the ER luminal chaperone BiP (a hallmark of ER stress), the UPR markers CHOP and ATF4, and the spliced form of XBP1. Pharmacological inhibition of UPR with chemical chaperone TUDC, or ATF4 silencing, resulted in impaired ERK5i-mediated UPR, autophagy and cytotoxicity. Overall, our results suggest that ERK5 inhibition induces autophagy-mediated cancer cell death by activating ER stress. Since ERK5 inhibition sensitizes cancer cells and tumors to chemotherapy, future work will determine the relevance of UPR and autophagy in the combined use of chemotherapy and ERK5i to tackle Cancer.

Sign in / Sign up

Export Citation Format

Share Document