Asset Details
Do you wish to reserve the book?
Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
Do you wish to request the book?
Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
2016
Overview
The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble protein-disulfide isomerase involved in ER protein folding and quality control, is secreted and interacts with the ECM. Extracellular AGR2 (eAGR2) is a microenvironmental regulator of epithelial tissue architecture, which plays a role in the preneoplastic phenotype and contributes to epithelial tumorigenicity. Indeed, eAGR2, is secreted as a functionally active protein independently of its thioredoxin-like domain (CXXS) and of its ER-retention domain (KTEL), and is sufficient, by itself, to promote the acquisition of invasive and metastatic features. Therefore, we conclude that eAGR2 plays an extracellular role independent of its ER function and we elucidate this gain-of-function as a novel and unexpected critical ECM microenvironmental pro-oncogenic regulator of epithelial morphogenesis and tumorigenesis. Cancer cells multiply abnormally fast and therefore produce protein molecules faster than normal cells. To avoid becoming stressed by this overproduction, cancer cells make use of proteins that fold the new proteins inside the cell. One of these protein folders is called anterior gradient-2 (or AGR2 for short) and is produced at high levels in so-called epithelial cancers, such as breast and lung cancer. Previous research has shown that AGR2 inside cancer cells can help them grow and survive and AGR2 can also be found outside cells, such as in the blood or the urine of cancer patients. Therefore some researchers have suggested that measuring the levels of AGR2 in bodily fluids may be a useful marker for detecting cancers. Fessart et al. hypothesized that – apart from becoming a promising diagnostic tool – the AGR2 protein itself, specifically when found outside cells, might make cancer cells more aggressive. Fessart et al. used a range of techniques to test this hypothesis. For example, healthy lung cells and lung cancer cells were grown into miniature replicas of lung organs in the laboratory, and in a key experiment, AGR2 was added to the lung organoids grown from the healthy cells. The addition of AGR2 protein was enough to change the non-tumor organoids into tumor organoids and boosted their growth about ten-fold. Further experiments then revealed that AGR2 also makes cells more invasive and capable of moving, both important features of aggressive cancer cells. Overall, Fessart et al. have proven that AGR2 is a signalling molecule found outside cancer cells that makes them more aggressive. In future, more research addressing how AGR2 achieves this may lead to new therapeutic strategies against some forms of cancer.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publication,eLife Sciences Publications, Ltd
