Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential

In eukaryotic cells, the endoplasmic reticulum (ER) is an organelle that is responsible for protein folding and assembly, lipid and sterol biosynthesis, and free calcium storage. In the past decade, intensive research effort has been focused on intracellular stress signaling pathways from the ER that lead to transcriptional and translational reprogramming of stressed cells. These signaling pathways, which are collectively termed Unfolded Protein Response (UPR), are critical for the cell to make survival or death decision under ER stress conditions. In recent years, research in the cancer field has revealed that ER stress and the UPR are highly induced in various tumors and are closely associated with cancer cell survival and resistance to anti-cancer treatments. Identifying the UPR components that are activated or suppressed in malignancy and exploring cancer therapeutic potentials by targeting the UPR are hot research spots. In this review, we summarize the recent progress in understating UPR signaling in cancer and its related therapeutic potential.