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.
Highlights
Endometrial cancer (EC) is the most frequent form of malignant tumor of the female reproductive tract, and overall the endometrium is the fourth most common cancer site, accounting for 6% of all women cancers [1, 2]
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
UPR ACTIVATION AND GRP78 IN ENDOMETRIAL CANCER We have recently reported for the first time that ER stress is activated in EC, as demonstrated by increased expression levels of activating transcription factor-6 (ATF6), GRP78, and CHOP/GADD153 in endometrioid carcinomas (EEC) tissues [31]
Summary
Reviewed by: Renato Franco, Istituto Tumori Fondazione Giovanni Pascale, Italy Sabrina Rossi, Treviso General Hospital, Italy. A restricted number of genes have been reported to be mutated in EC, mediating cell proliferation and invasiveness 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. 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, GRP78 might constitute a novel target for the treatment of EC in combination with traditional adjuvant therapy
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