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.

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 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 LIFR-AS1 modulates Sufu to inhibit cell proliferation and migration by miR-197-3p in breast cancer

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Fangfang Xu ◽  
Hui Li ◽  
Chengjiu Hu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Colony Formation ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Wide Range

AbstractNumerous evidence has recently demonstrated that long non-coding RNAs (lncRNAs) play vital roles in the oncogenesis and development of a wide range of human neoplasms. Leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1), a novel cancer-related lncRNA, has been reported to be under-expressed in breast cancer and associated with poor prognosis. However, the exact role of LIFR-AS1 in breast cancer remains largely unclear. The present study aimed to investigate the biological role of LIFR-AS1 in breast cancer and clarify the potential molecular mechanisms. In the present study, we found that LIFR-AS1 was significantly down-regulated in both tissues and cell lines. Furthermore, over-expression of LIFR-AS1 inhibited breast cancer cell proliferation, colony formation, migration and invasion, whereas knockdown of LIFR-AS1 promoted breast cancer cell proliferation, colony formation, migration and invasion. Moreover, LIFR-AS1 was observed to up-regulate suppressor of fused gene (Sufu) expression by competitively binding to miR-197-3p in breast cancer cells. Notably, miR-197-3p inhibitor reversed the promoting effects of LIFR-AS1 knockdown on breast cancer cell proliferation, colony formation, migration and invasion. Additionally, LIFR-AS1 knockdown promoted tumor growth in vivo. To sum up, our results imply the tumor-suppressing role of LIFR-AS1 in breast cancer.

Evidence that TRPM7 is required for breast cancer cell proliferation

2009 ◽  
Vol 297 (3) ◽  
pp. C493-C502 ◽  
Author(s):  
Arnaud Guilbert ◽  
Mathieu Gautier ◽  
Isabelle Dhennin-Duthille ◽  
Nathalie Haren ◽  
Henri Sevestre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Human Breast ◽  
Breast Cancer Cell Proliferation ◽  
Inward Current ◽  
Mcf 7

Because transient receptor potential (TRP) channels have been implicated in tumor progression, we have investigated the potential role of TRPM7 channel in breast cancer cell proliferation. Under whole cell patch clamp, a Mg2+-inhibited cationic (MIC) current was observed in MCF-7 cells. This current was characterized by an inward current and a strong outward rectifying current that were both inhibited in a concentration-dependent manner by the presence of intracellular Mg2+ or Mg2+-ATP. The inward current was reduced by La3+, and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La3+, and flufenamic acid. Importantly, a similar MIC current was also recorded in the primary culture of human breast cancerous epithelial cells (hBCE). Moreover, TRPM7 transcripts were found in both hBCE and MCF-7 cells. In MCF-7 cells, the MIC current was inhibited by TRPM7 small interfering RNA. Interestingly, we found that cell proliferation and intracellular Ca2+ concentration were also reduced by TRPM7 silencing in MCF-7 cells. TRPM7 channels were also found in both human breast cancer and healthy tissues. Importantly, TRPM7 channel was overexpressed in grade III breast cancer samples associated with important Ki67 or tumor size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating Ca2+ influx.

Madhuca indica Inhibits Breast Cancer Cell Proliferation by Modulating COX-2 Expression

2019 ◽  
Vol 18 (7) ◽  
pp. 459-474 ◽  
Author(s):  
Paramita Ghosh ◽  
Debarpan Mitra ◽  
Sreyashi Mitra ◽  
Sudipta Ray ◽  
Samir Banerjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cox 2

Characterization of YY1 OPB Peptide for its Anticancer Activity

2019 ◽  
Vol 19 (6) ◽  
pp. 504-511 ◽  
Author(s):  
Yige Qi ◽  
Ting Yan ◽  
Lu Chen ◽  
Qiang Zhang ◽  
Weishu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acids ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Expression Vectors ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Oncogene Products ◽  
And Migration

Background:The oncoprotein binding (OPB) domain of Yin Yang 1 (YY1) consists of 26 amino acids between G201 and S226, and is involved in YY1 interaction with multiple oncogene products, including MDM2, AKT, EZH2 and E1A. Through the OPB domain, YY1 promotes the oncogenic or proliferative regulation of these oncoproteins in cancer cells. We previously demonstrated that a peptide with the OPB sequence blocked YY1-AKT interaction and inhibited breast cancer cell proliferation.Objective:In the current study, we characterized the OPB domain and determined a minimal region for peptide design to suppress cancer cellMethods:Using alanine-scan method, we identified that the amino acids at OPB C-terminal are essential to YY1 binding to AKT. Further studies suggested that serine and threonine residues, but not lysines, in OPB play a key role in YY1-AKT interaction. We generated GFP fusion expression vectors to express OPB peptides with serially deleted N-terminal and found that OPB1 (i.e. G201-S226) is cytoplasmic, but OPB2 (i.e. E206-S226), OPB3 (i.e. E206-S226) and control peptide were both nuclear and cytoplasmic.Results:Both OPB1 and 2 inhibited breast cancer cell proliferation and migration, but OPB3 exhibited similar effects to control. OPB1 and 2 caused cell cycle arrest at G1 phase, increased p53 and p21 expression, and reduced AKT(S473) phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells.Conclusion:: Overall, the serines and threonines of OPB are essential to YY1 binding to oncoproteins, and OPB peptide can be minimized to E206-S226 that maintain inhibitory activity to YY1- promoted cell proliferation.

The epithelial sodium channel has a role in breast cancer cell proliferation

2021 ◽  
Vol 187 (1) ◽  
pp. 31-43
Author(s):  
Adam W. Ware ◽  
Joshua J. Harris ◽  
Tania L. Slatter ◽  
Heather E. Cunliffe ◽  
Fiona J. McDonald
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Sodium Channel ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Epithelial Sodium Channel ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation
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