GRP78 induced by estrogen plays a role in the chemosensitivity of endometrial cancer

Luvsandagva, Baigalimaa; Nakamura, Kazuto; Kitahara, Yoshikazu; Aoki, Hiroshi; Murata, Tomomi; Ikeda, Sadatomo; Minegishi, Takashi

doi:10.1016/j.ygyno.2012.04.025

Cited by 27 publications

(21 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This highlighted marked explanations to the epidemiological mystery that the incidence of gastric cancer in males has been considerably higher than that in females. In addition, estrogen may induce GRP78, which has been found to correlate with cell viability and resistance to paclitaxel and cisplatin in endometrial cancer (11). Administration of a small volume of E2, prolonged the survival of rats by 3 h by ameliorating endoplasmic reticulum stress (12).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Estrogen protects SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by the Akt pathway

Feng

Deng

et al. 2013

Oncology Letters

View full text Add to dashboard Cite

Several previous studies have demonstrated that estrogen may protect cancer cells from endoplasmic reticulum stress-induced apoptosis. However, the molecular mechanisms involved are not fully understood. In the present study, human gastric adenocarcinoma SGC7901 cells were treated with tunicamycin (TM) to induce endoplasmic reticulum stress. This was demonstrated by increased glucose-regulated protein 78 expression and enhanced phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase. Endoplasmic reticulum stress induced caspase-3-mediated apoptosis with the inhibition of Akt; the latter of which was measured by the activity-dependent phosphorylation at Ser473 of Akt. Simultaneous treatment of 10−9 M 17β-estradiol (E2) with TM may protect SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by counteracting the inhibitory effect of TM on Akt, causing an increase in the phosphorylation of Ser473-Akt. It was concluded that low concentrations of E2 may counteract endoplasmic reticulum stress-induced inactivation of Akt to block caspase-3-mediated apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Estrogen may induce GRP78, which has been found to correlate with cell viability and resistance to paclitaxel and cisplatin in endometrial cancer (11). Administration of a small volume of 17β-estradiol (E2)prolonged the survival of rats by 3 h by ameliorating endoplasmic reticulum stress (12).…”

Section: Introductionmentioning

confidence: 99%

Estrogen protects SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by the Akt pathway

Feng

Deng

et al. 2013

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…The UPR is upregulated in many cancers and is an important contributor to tumor development and maintenance (182–184). ER stress sensitizes cells to a broad range of chemotherapeutics including topoisomerase inhibitors (185), temozolomide (186), platinum-based agents (187, 188), and TBAs (189). …”

Section: Microtubule Cytoskeleton In Stress Responsesmentioning

confidence: 99%

Microtubules and Their Role in Cellular Stress in Cancer

2014

View full text Add to dashboard Cite

Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking, and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However, the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule–protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer.

show abstract

“…It appears important to note that estrogen is strongly associated with chemoresistance mechanisms in both endometrial and ovarian cancers [148–150]. It has been demonstrated in endometrial cancer cells that estrogen can positively activate GRP78, thus preventing apoptosis and providing chemoresistance to both paclitaxel and cisplatin [149]. Another study demonstrated that estrogen can provide chemoresistance to paclitaxel treatment in ovarian cancer cells via the phosphorylation of AKT-ASK1 complex [150].…”

Section: Chemoresistance In Gynecological Cancersmentioning

confidence: 99%

Chemoresistance and targeted therapies in ovarian and endometrial cancers

2016

View full text Add to dashboard Cite

Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4). To overcome these resistances, a new type of therapy has emerged named targeted therapy. The principle of targeted therapy is simple, taking advantage of changes acquired in malignant cancer cells (receptors, proteins, mechanisms) by using compounds specifically targeting these, thus limiting their action on healthy cells. Targeted therapies are emerging and many clinical trials targeting these pathways, frequently involved in chemoresistance, have been tested on gynecological cancers. Despite some targets being less efficient than expected as mono-therapies, the combination of compounds seems to be the promising avenue. For instance, we demonstrate using ChIP-seq analysis that estrogen downregulate tumor suppressor Par-4 in hormone-dependent cells by directly binding to its DNA regulatory elements and inhibiting estrogen signaling could reinstate Par-4 apoptosis-inducing abilities. This review will focus on the chemoresistance mechanisms and the clinical trials of targeted therapies associated with these, specifically for endometrial and ovarian cancers.

show abstract

GRP78 induced by estrogen plays a role in the chemosensitivity of endometrial cancer

Cited by 27 publications

References 39 publications

Estrogen protects SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by the Akt pathway

Estrogen protects SGC7901 cells from endoplasmic reticulum stress-induced apoptosis by the Akt pathway

Microtubules and Their Role in Cellular Stress in Cancer

Chemoresistance and targeted therapies in ovarian and endometrial cancers

Contact Info

Product

Resources

About