scholarly journals AGR3 promotes estrogen receptor‑positive breast cancer cell proliferation in an estrogen‑dependent manner

2020 ◽  
Vol 20 (2) ◽  
pp. 1441-1451
Author(s):  
Lei Jian ◽  
Jian Xie ◽  
Shipeng Guo ◽  
Haochen Yu ◽  
Rui Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Breast Cancer Cell ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer Cell ◽  
Positive Breast Cancer

scholarly journals OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Jianing Tang ◽  
Zeyu Wu ◽  
Zelin Tian ◽  
Wei Chen ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Estrogen Receptor Α ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Positive Breast Cancer

AbstractBreast cancer is the most common malignancy in women worldwide. Estrogen receptor α (ERα) is expressed in ∼70% of breast cancer cases and promotes estrogen-dependent cancer progression. In the present study, we identified OTU domain-containing 7B (OTUD7B), a deubiquitylase belonging to A20 subgroup of ovarian tumor protein superfamily, as a bona fide deubiquitylase of ERα in breast cancer. OTUD7B expression was found to be positively correlated with ERα in breast cancer and associated with poor prognosis. OTUD7B could interact with, deubiquitylate, and stabilize ERα in a deubiquitylation activity-dependent manner. Depletion of OTUD7B decreased ERα protein level, the expression of ERα target genes, and the activity of estrogen response element in breast cancer cells. In addition, OTUD7B depletion significantly decreased ERα-positive breast cancer cell proliferation and migration. Finally, overexpression of ERα could rescue the suppressive effect induced by OTUD7B depletion, suggesting that the ERα status was essential to the function of OTUD7B in breast carcinogenesis. In conclusion, our study revealed an interesting post-translational mechanism between ERα and OTUD7B in ERα-positive breast cancer. Targeting the OTUD7B–ERα complex may prove to be a potential approach to treat patients with ERα-positive breast cancer.

scholarly journals A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation

2019 ◽  
Vol 47 (18) ◽  
pp. 9557-9572 ◽  
Author(s):  
Gozde Korkmaz ◽  
Zohar Manber ◽  
Rui Lopes ◽  
Stefan Prekovic ◽  
Karianne Schuurman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Hormonal Treatment ◽  
Ctcf Binding ◽  
Chromatin Conformation ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation

Abstract Estrogen receptor α (ERα) is an enhancer activating transcription factor, a key driver of breast cancer and a main target for cancer therapy. ERα-mediated gene regulation requires proper chromatin-conformation to facilitate interactions between ERα-bound enhancers and their target promoters. A major determinant of chromatin structure is the CCCTC-binding factor (CTCF), that dimerizes and together with cohesin stabilizes chromatin loops and forms the boundaries of topologically associated domains. However, whether CTCF-binding elements (CBEs) are essential for ERα-driven cell proliferation is unknown. To address this question in a global manner, we implemented a CRISPR-based functional genetic screen targeting CBEs located in the vicinity of ERα-bound enhancers. We identified four functional CBEs and demonstrated the role of one of them in inducing chromatin conformation changes in favor of activation of PREX1, a key ERα target gene in breast cancer. Indeed, high PREX1 expression is a bona-fide marker of ERα-dependency in cell lines, and is associated with good outcome after anti-hormonal treatment. Altogether, our data show that distinct CTCF-mediated chromatin structures are required for ERα- driven breast cancer cell proliferation.

scholarly journals Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation

Endocrinology ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 4218-4232 ◽  
Author(s):  
Chikayo Iwaya ◽  
Takashi Nomiyama ◽  
Shiho Komatsu ◽  
Takako Kawanami ◽  
Yoko Tsutsumi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Tissue ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Mcf 7

Abstract Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

scholarly journals p53–GSDME Elevation: A Path for CDK7 Inhibition to Suppress Breast Cancer Cell Survival

2021 ◽  
Vol 8 ◽  
Author(s):  
Yueyuan Wang ◽  
Jingyu Peng ◽  
Xuguang Mi ◽  
Ming Yang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Survival ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Colony Formation ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Cell Survival

Higher cyclin-dependent kinase (CDK7) expression is a character of breast cancer and indicates poor prognosis. Inhibiting CDK7 exhibited effective cancer cell suppression which implies the potential of CDK7 inhibition to be a method for anti-cancer treatment. Our study aimed to explore a novel mechanism of CDK7 inhibition for suppressing breast cancer cell survival. Here, we proved inhibiting CDK7 repressed breast cancer cell proliferation and colony formation and increased the apoptotic cell rate, with p53 and GSDME protein level elevation. When p53 was suppressed in MCF-7 cells, the decline of GSDME expression and associated stronger proliferation and colony formation could be observed. Since downregulation of GSDME was of benefit to breast cancer cells, p53 inhibition blocked the elevation of GSDME induced by CDK7 inhibition and retrieved cells from the tumor suppressive effect of CDK7 inhibition. Therefore, CDK7 inhibition exerted a negative effect on breast cancer cell proliferation and colony formation in a p53–GSDME dependent manner. These results revealed the CDK7–p53–GSDME axis could be a pathway affecting breast cancer cell survival.

Sign in / Sign up

Export Citation Format

Share Document