Frontiers in Pharmacology (Sep 2021)
Targeting the Integrated Stress Response in Cancer Therapy
- Xiaobing Tian,
- Xiaobing Tian,
- Xiaobing Tian,
- Xiaobing Tian,
- Shengliang Zhang,
- Shengliang Zhang,
- Shengliang Zhang,
- Shengliang Zhang,
- Lanlan Zhou,
- Lanlan Zhou,
- Lanlan Zhou,
- Lanlan Zhou,
- Attila A. Seyhan,
- Attila A. Seyhan,
- Attila A. Seyhan,
- Attila A. Seyhan,
- Liz Hernandez Borrero,
- Yiqun Zhang,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry
Affiliations
- Xiaobing Tian
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Xiaobing Tian
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Xiaobing Tian
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Xiaobing Tian
- Cancer Center at Brown University, Providence, RI, United States
- Shengliang Zhang
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Shengliang Zhang
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Shengliang Zhang
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Shengliang Zhang
- Cancer Center at Brown University, Providence, RI, United States
- Lanlan Zhou
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Lanlan Zhou
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Lanlan Zhou
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Lanlan Zhou
- Cancer Center at Brown University, Providence, RI, United States
- Attila A. Seyhan
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Attila A. Seyhan
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Attila A. Seyhan
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Attila A. Seyhan
- Cancer Center at Brown University, Providence, RI, United States
- Liz Hernandez Borrero
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Yiqun Zhang
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Cancer Center at Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Hematology/Oncology Division, Department of Medicine, Lifespan Health System and Brown University, Providence, RI, United States
- DOI
- https://doi.org/10.3389/fphar.2021.747837
- Journal volume & issue
-
Vol. 12
Abstract
The integrated stress response (ISR) is an evolutionarily conserved intra-cellular signaling network which is activated in response to intrinsic and extrinsic stresses. Various stresses are sensed by four specialized kinases, PKR-like ER kinase (PERK), general control non-derepressible 2 (GCN2), double-stranded RNA-dependent protein kinase (PKR) and heme-regulated eIF2α kinase (HRI) that converge on phosphorylation of serine 51 of eIF2α. eIF2α phosphorylation causes a global reduction of protein synthesis and triggers the translation of specific mRNAs, including activating transcription factor 4 (ATF4). Although the ISR promotes cell survival and homeostasis, when stress is severe or prolonged the ISR signaling will shift to regulate cellular apoptosis. We review the ISR signaling pathway, regulation and importance in cancer therapy.
Keywords
