Dual RNase activity of IRE1 as a target for anticancer therapies.
Sylwia BartoszewskaJakub SławskiJames F CollawnRafał BartoszewskiPublished in: Journal of cell communication and signaling (2023)
The unfolded protein response (UPR) is a cellular mechanism that protects cells during stress conditions in which there is an accumulation of misfolded proteins in the endoplasmic reticulum (ER). UPR activates three signaling pathways that function to alleviate stress conditions and promote cellular homeostasis and cell survival. During unmitigated stress conditions, however, UPR activation signaling changes to promote cell death through apoptosis. Interestingly, cancer cells take advantage of this pathway to facilitate survival and avoid apoptosis even during prolonged cell stress conditions. Here, we discuss different signaling pathways associated with UPR and focus specifically on one of the ER signaling pathways activated during UPR, inositol-requiring enzyme 1α (IRE1). The rationale is that the IRE1 pathway is associated with cell fate decisions and recognized as a promising target for cancer therapeutics. Here we discuss IRE1 inhibitors and how they might prove to be an effective cancer therapeutic.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- endoplasmic reticulum
- cell cycle arrest
- cell death
- signaling pathway
- pi k akt
- papillary thyroid
- oxidative stress
- cell fate
- stress induced
- clinical trial
- small molecule
- protein protein
- bone marrow
- squamous cell carcinoma
- cell proliferation
- childhood cancer
- cell therapy
- mesenchymal stem cells
- lymph node metastasis
- heat stress
- young adults
- binding protein