Journal of cell science
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Journal of cell science · Sep 2013
The ire-1 ER stress-response pathway is required for normal secretory-protein metabolism in C. elegans.
The unfolded protein response (UPR) allows cells to cope with endoplasmic reticulum (ER) stress by adjusting the capacity of the ER to the load of ER-associated tasks. The UPR is important for maintaining ER homeostasis under extreme ER stress. UPR genes are important under normal growth conditions as well, but what they are required for under these conditions is less clear. ⋯ Notably, by compromising ER-associated degradation (ERAD) and phagocytosis, loss of ire-1 hinders the clearance of misfolded proteins from the ER as well as the clearance of proteins that were secreted into the pseudocoleom. Whereas the basal activity of the UPR is beneficial under normal conditions, it accelerates the pathology caused by toxic Aβ protein in a C. elegans model of Alzheimer's disease. Taken together, our findings indicate that UPR genes are critical for maintaining secretory protein metabolism under normal growth conditions.
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Journal of cell science · Sep 2013
MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer stem cells.
Human gastric cancers contain a population of gastric cancer stem cells (GCSCs) that can undergo self-renewal and multipotent differentiation. GCSCs can be enriched with EpCAM+/CD44+ gastric cancer cells. However, the underlying mechanisms controlling the balance of GCSC self-renewal and differentiation remain to be explored. ⋯ Furthermore, we found that miR-19b, miR-20a and miR-92a could also promote the proliferation of gastric cancer cells. miR-17-92 targeted the E2F1 and HIPK1 proteins, which suppressed Wnt-β-catenin signaling. A real-time PCR analysis of miR-19b, miR-20a and miR-92a expression in 97 gastric cancer specimens suggested that miR-92a could be used as an independent prognostic factor in gastric cancer. This study showed that several members of the miR-17-92 cluster, miR-19b, miR-20a and miR-92a, might play important roles in the development of gastric cancer stem cells and that miR-92a has the potential to be used as a predictive prognostic marker in gastric cancer.