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Updated: May 8, 2026

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
IRE1α-mediated UPR activation in gastrointestinal cancers: Adaptive mechanisms and therapeutic potential
Valappan Veetil Soumya1, Baby Jisna1, Davis Anu1
1Department of Biochemistry, Amala Cancer Research Centre (Recognised Research Centre, University of Calicut), Thrissur - 680 555, Kerala, India.
Abstract:
The endoplasmic reticulum (ER) plays a crucial role in protein synthesis, folding and quality control. Disruptions in these processes lead to ER stress (ERS) and activate the unfolded protein response (UPR) to restore cellular homeostasis. In gastrointestinal cancers, inositol-requiring enzyme 1α (IRE1α) is a key regulator of the UPR, enabling cancer cells to adapt to hostile conditions such as hypoxia, oxidative stress and chemotherapy. Elevated IRE1α activity supports tumor survival, progression and metastasis by mitigating ERS-induced apoptosis. However, targeting IRE1α signaling presents a promising therapeutic strategy by impairing cancer cell adaptation to stress, offering promising therapeutic opportunities for gastrointestinal cancers.
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