Endoplasmic reticulum stress in endometrial cancer

Abstract

Endometrial cancer (EC) is a common gynecologic malignancy often diagnosed at early stage. In spite of a huge advance in our understanding of EC biology, therapeutic modalities do not have significantly changed over the past 40 years. A restricted number of genes have been reported to be mutated in EC, mediating cell proliferation and invasiveness. However, besides these alterations, few other groups and ourselves recently identified the activation of the unfolded protein response (UPR) and GRP78 increase following endoplasmic reticulum (ER) stress as mechanisms favoring growth and invasion of EC cells. Here, a concise update on currently available data in the field is presented, analyzing the crosstalk between the UPR and the main signaling pathways regulating EC cell proliferation and survival. It is evident that this is a rapidly expanding and promising issue. However, more data are very likely to yield a better understanding on the mechanisms through which EC cells can survive the low oxygen and glucose tumor microenvironment. In this perspective, the UPR and, particularly, GRP78 might constitute a novel target for the treatment of EC in combination with traditional adjuvant therapy.

Keywords: GRP78; UPR; endometrial cancer; endoplasmic reticulum; stress.

Figure 1

Microenvironmental stress causes ER stress and UPR activation in cancer cells. As a result, GRP78 is upregulated to enhance the folding capacity of the ER. A quote of the protein is transported to the cell membrane where it can bind different molecular partners and transduce either pro-survival or apoptotic signals.