ER stress mediated inflammation in cancer pathogenesis

Soumya S. Jalajakumari, Renu Ramesh, Achuthsankar S. Nair

Article ID: 2531
Vol 8, Issue 1, 2024

VIEWS - 484 (Abstract) 301 (PDF)

Abstract


Inflammation is a complex process which is associated with the initiation and progression of cancer. Prolonged Endoplasmic Reticulum (ER) stress triggers inflammation which is a key factor associated with cancer pathogenesis. ER stress also contributes to immune suppression in inflammatory and tumor microenvironment. It stimulates the production of pro-inflammatory cytokines by regulating the activation of various transcription factors and inflammatory signalling pathways. Targeting ER stress is an exciting possibility that can be used as a therapeutic strategy for cancer treatment. This mini review focuses on the emerging link between ER stress-induced inflammatory responses in cancer development.


Keywords


ER stress; inflammation; cancer; UPR response

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References


1. Berridge MJ. The endoplasmic reticulum: A multifunctional signaling organelle. Cell Calcium, Endoplasmic Reticulum as a Signalling Organelle 2002; 32(5–6): 235–249. doi: 10.1016/S0143416002001823

2. Grandjean JMD, Wiseman RL. Small molecule strategies to harness the unfolded protein response: where do we go from here? Journal of Biological Chemistry 2020; 295(46): 15692–15711. doi: 10.1074/jbc.REV120.010218

3. Li Y, Lu L, Zhang G, et al. The role and therapeutic implication of endoplasmic reticulum stress in inflammatory cancer transformation. American Journal of Cancer Research 2022; 12(5): 2277–2292.

4. Hetz C, Zhang K, Kaufman RJ. Mechanism, regulation and functions of the unfolded protein response. Nature Reviews. Molecular Cell Biology 2020; 21(8): 421–438. doi: 10.1038/s41580-020-0250-z

5. Papaioannou A, Chevet E. Driving cancer tumorigenesis and metastasis through UPR signaling. In: Wiseman RL, Haynes CM (editors). Coordinating Organismal Physiology through the Unfolded Protein Response, Current Topics in Microbiology and Immunology. Springer International Publishing, Cham; 2018; 414:159–192.

6. Rutkowski DT, Kaufman RJ. A trip to the ER: Coping with stress. Trends in Cell Biology 2004; 14: 20–28. doi: 10.1016/j.tcb.2003.11.001

7. Jaramillo MC, Zhang DD. The emerging role of the Nrf2–Keap1 signaling pathway in cancer. Genes & Development 2013; 27(20): 2179–2191. doi: 10.1101/gad.225680.113

8. Koromilas AE. Roles of the translation initiation factor eIF2α serine 51 phosphorylation in cancer formation and treatment. Biochim. Biophys. Acta (BBA)—Gene Regulatory Mechanisms 2015; 1849(7): 871–880. doi: 10.1016/j.bbagrm.2014.12.007

9. Verfaillie T, Garg AD, Agostinis P. Targeting ER stress induced apoptosis and inflammation in cancer. Cancer Letters 2013; 332(2): 249–264. doi: 10.1016/j.canlet.2010.07.016

10. Manna SK, Babajan B, Raghavendra PB, et al. Inhibiting TRAF2- ediated activation of NF-kappaB facilitates induction of AP-1. Journal of Biological Chemistry 2010; 285(15): 11617–11627. doi: 10.1074/jbc.m109.094961

11. Currò M, Gangemi C, Giunta ML, et al. Transglutaminase 2 is involved in amyloid-beta 1–42-induced proinflammatory activation via AP1/JNK signalling pathways in THP-1 monocytes. Amino Acids 2016; 49(3): 659–669. doi: 10.1007/s00726-016-2366-1

12. Mahadevan NR, Rodvold J, Almanza G, Pérez AF, Wheeler MC, Zanetti M. ER stress drives Lipocalin 2 upregulation in prostate cancer cells in an NF-κB-dependent manner. BMC Cancer. 2011 Jun 7;11:229. doi: 10.1186/1471-2407-11-229.

13. Swanson KV, Deng M, Ting JPY. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nature Reviews Immunology 2019; 19(8): 477–489. doi: 10.1038/s41577-019-0165-0

14. Carothers AM, Davids JS, Damas BC, Bertagnolli MM. Persistent cyclooxygenase-2 inhibition downregulates NF-{kappa}B, resulting in chronic intestinal inflammation in the min/+mouse model of colon tumorigenesis. Cancer Research 2010; 70(11): 4433–4442. doi: 10.1158/0008-5472.CAN-09-4289

15. Liu X, Plummer SJ, Nock NL, et al. Nonsteroidal antiinflammatory drugs and decreased risk of advanced prostate cancer: Modification by lymphotoxin alpha. American Journal of Epidemiology 2006; 164(10): 984–989. doi: 10.1093/aje/kwj294

16. Luo JL, Maeda S, Hsu LC, et al. Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAILmediated tumor regression. Cancer Cell 2004; 6(3): 297–305. doi: 10.1016/j.ccr.2004.08.012

17. Gierach GL, Lacey JV, Schatzkin A, et al. Nonsteroidal anti-inflammatory drugs and breast cancer risk in the national contribution of ER stress to immunogenic cancer cell death institutes of Health-AARP diet and health study. Breast Cancer Research 2008; 10(2): R38. doi: 10.1186/bcr2089

18. Ojha R, Amaravadi RK. Targeting the unfolded protein response in cancer. Pharmacological Research 2017; 120: 258–266. doi: 10.1016/j.phrs.2017.04.003

19. Garg AD, Krysko DV, Golab J, et al. Contribution of ER stress to immunogenic cancer cell death. In: Agostinis P, Afshin S (editors). Endoplasmic Reticulum Stress in Health and Disease. Springer; 2012.

20. Axten JM, Romeril SP, Shu A, et al. Discovery of GSK2656157: An optimized PERK inhibitor selected for preclinical development. ACS Medicinal Chemistry Letters 2013; 4(10): 964–968. doi: 10.1021/ml400228e

21. Atkins C, Liu Q, Minthorn E, et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Research 2013; 73(6): 1993–2002. doi: 10.1158/0008-5472.CAN-12-3109




DOI: https://doi.org/10.24294/ti.v8.i1.2531

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