Cells' Secret Weapon: The ER's Hidden Role in Cancer Survival

The endoplasmic reticulum (ER) is a crucial part of cells. It handles the folding and secretion of a significant portion of proteins in eukaryotic cells. Stress can disrupt this process, leading to misfolded proteins and ER stress. Cells have ways to manage this stress, such as reducing the protein load in the ER. One newly discovered method involves sending proteins from the ER back to the cell's main body, the cytosol. This process, called ERCYS, gives these proteins new life-sustaining roles in cancer cells, boosting their ability to survive. Inside mammalian cells, ERCYS is controlled by specific proteins: DNAJB12, DNAJB14, and a helper protein called SGTA. These proteins work together to move ER proteins back to the cytosol. DNAJB12 and DNAJB14 have parts that bind to HSC70 and SGTA, making this movement possible. DNAJB12 is particularly important. It helps increase the reflux of a protein called AGR2 and stops a tumor-suppressing protein, wt-p53, from doing its job during ER stress. If DNAJB12 or DNAJB14 is mutated, this process is disrupted, and wt-p53 can function normally. This discovery opens up new possibilities for cancer treatment. By targeting the interaction between DNAJB12/14, HSC70, and SGTA, it might be possible to stop ERCYS. This could weaken cancer cells and make them more susceptible to treatment. However, more research is needed to fully understand this process and develop effective therapies. It's a complex web of interactions, and scientists are still unraveling the details. The ER is often overlooked in discussions about cancer. But its role in protein processing and stress response makes it a key player in cancer cell survival. Understanding how the ER adapts to stress could provide new insights into cancer biology and treatment. It's a reminder that even the most well-studied cellular structures can still hold surprises.