scholarly journals USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3090
Author(s):  
Ashley Mussell ◽  
He Shen ◽  
Yanmin Chen ◽  
Michalis Mastri ◽  
Kevin H. Eng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Protein Stability ◽  
Cancer Patients ◽  
Effector Proteins ◽  
Therapeutic Interventions ◽  
Hippo Signaling ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
Loss Of Function

The Hippo signaling pathway is an evolutionarily conserved pathway that was initially discovered in Drosophila melanogaster and was later found to have mammalian orthologues. The key effector proteins in this pathway, YAP/TAZ, are often dysregulated in cancer, leading to a high degree of cell proliferation, migration, metastasis and cancer stem cell populations. Due to these malignant phenotypes it is important to understand the regulation of YAP/TAZ at the protein level. Using an siRNA library screen of deubiquitinating enzymes (DUBs), we identified ubiquitin specific peptidase 1 (USP1) as a novel TAZ (WWTR1) regulator. We demonstrated that USP1 interacts with TAZ and increases TAZ protein stability. Conversely, loss of function of USP1 reduces TAZ protein levels through increased poly-ubiquitination, causing a decrease in cell proliferation and migration of breast cancer cells. Moreover, we showed a strong positive correlation between USP1 and TAZ in breast cancer patients. Our findings facilitate the attainment of better understanding of the crosstalk between these pathways and may lead to potential therapeutic interventions for breast cancer patients.

Correlation of AGR2 expression with the incidence of metastasis in luminal breast cancer

2021 ◽  
pp. 1-5
Author(s):  
David Samuel Kereh ◽  
John Pieter ◽  
William Hamdani ◽  
Haryasena Haryasena ◽  
Daniel Sampepajung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mean Value ◽  
Rank Test ◽  
Luminal Breast Cancer ◽  
P Value ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
The Mean ◽  
Spearman Test

BACKGROUND: AGR2 expression is associated with luminal breast cancer. Overexpression of AGR2 is a predictor of poor prognosis. Several studies have found correlations between AGR2 in disseminated tumor cells (DTCs) in breast cancer patients. OBJECTIVE: This study aims to determine the correlation between anterior Gradient2 (AGR2) expression with the incidence of distant metastases in luminal breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and the network. ELISA methods examine AGR2 expression from blood serum of breast cancer patients. To compare the AGR2 expression in metastatic patients and the non-metastatic patient was tested with Mann Whitney test. The correlation of AGR2 expression and metastasis was tested with the Rank Spearman test. RESULTS: The mean value of AGR2 antibody expression on ELISA in this study was 2.90 ± 1.82 ng/dl, and its cut-off point was 2.1 ng/dl. Based on this cut-off point value, 14 subjects (66.7%) had overexpression of AGR2 serum ELISA, and 7 subjects (33.3%) had not. The mean value AGR2 was significantly higher in metastatic than not metastatic, 3.77 versus 1.76 (p < 0.01). The Spearman rank test obtained a p-value for the 2 tail test of 0.003 (p < 0.05), which showed a significant correlation of both, while the correlation coefficient of 0.612 showed a strong positive correlation of AGR2 overexpression and metastasis. CONCLUSIONS: AGR2 expression is correlated with metastasis in Luminal breast cancer.

Prognostic value of vascular density and cell proliferation in breast cancer patients

1999 ◽  
Vol 195 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Olli Tynninen ◽  
Kristina von Boguslawski ◽  
Hannu J. Aronen ◽  
Timo Paavonen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Vascular Density ◽  
Breast Cancer Patients

Germline mutations of PALB2 gene in a sequential series of Chinese patients with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1530-1530
Author(s):  
Jiaojiao Zhou ◽  
Kun Zhang ◽  
Xuan Zhu ◽  
Mei Deng ◽  
Meng Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Germline Mutation ◽  
Familial Breast Cancer ◽  
Sporadic Breast Cancer ◽  
Critical Role ◽  
Germline Mutations ◽  
Chinese Patients ◽  
Breast Cancer Patients ◽  
Loss Of Function

1530 Background: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene, which plays a critical role in genome maintenance via interacting with BRCA1/2 and RAD51 when DNA break. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. Therefore, we assessed the mutational frequency, spectrum and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank, to verify the utility of PALB2 genetic testing in Chinese population. Methods: We examined Chinese breast cancer cases (n = 2279) who agreed to participate in research DNA banking, recruited from 1990 through 2016. To identify the mutations, complete coding sequence and intron–exon boundaries of PALB2 were screened with Next Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. Results: Among the 2279 breast cancer patients, 307 patients were familial breast cancer cases and the rest 1972 patients were sporadic breast cancer cases. PALB2 mutation carriers accounted for 7.8% (n = 24) and 4.8% (n = 95) in familial and sporadic breast cancer cohort separately. In total, 31 missense, 4 nonsense, 3 frameshift, 3 splicing and 1 codon mutations of PALB2 were identified in this study. Among the pathologic variants, PALB2 c.1744C > T, c.2748+1G > A, c.2749-1G > C, c.3114-1G > A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, a total of 6 potential damaging missense variants were novelly found in this study, among which the PALB2 c.3035C > T was detected in both sporadic and familial breast cancer. Conclusions: Our data presents the germline mutation status of PALB2 in Chinese patients with breast cancer, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, this information may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.

scholarly journals Exploration of Binding Interaction of Steroidal Drugs with HMG-CoA Reductase for the Treatment of Breast Cancer Patients who suffer with Cardiovascular Problems: In-silico Studies

2020 ◽  
Vol 5 (1) ◽  
pp. 27-33
Author(s):  
Varish Ahmad
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Cholesterol Synthesis ◽  
Breast Cancer Patients ◽  
Binding Interaction ◽  
Hmg Coa Reductase ◽  
Study Results ◽  
In Silico Studies ◽  
Coa Reductase

Introduction: HMG-CoA reductase is widely used as a significant target to screen cardiovascular therapeutics molecules because of its involvement in cholesterol synthesis and cell proliferation. Steroidal drugs like anastrozole, exemestane, letrozole have been tested as potential inhibitors of cancer mediated aromatase enzyme and these could be inhibited to HMG-CoA reductase so that the link with cholesterol synthesis and cell proliferation can be utilized to control cancers in. Objective: To test the binding affinity and binding patterns using computational methods of these drugs and established them as a HMG-CoA reductase inhibitor due to the involvement of this enzyme with cholesterol synthesis and cell proliferation can be utilized to control the cancers. Materials and methods: Freely available docking tools like AutoDock and web resources like DrugBank and PDB were used to extract data and conduct the study. Results: The binding interaction of exemestane has shown significant docking interactions which are followed by anastrozole and letrozole. Exemestane has shown binding energy -8.74 kcal/mol, hydrogen bond length: 1.97513 Å, and interacting amino acid was analyzed as A: ASN658:HD21-: UNK1: O6. The positive control statin was used in this study has shown significant binding interaction but it was less than tested exemestane.Conclusion: Thus, exemestane can potentially inhibit to HMG-CoA reductase enzyme even stronger than the clinically tested drug statin and would be a good choice for cancer patients. Thus, in vitro laboratory experimentation and in vivo research are necessary to put forward therapeutic repositioning of these drugs so they could be established as a broad spectrum potential anticancer drugs including breast cancer especially for the patient with cardiovascular complications.  

scholarly journals Metformin Efficacy on Proliferation Indices of Tumoral Cells in Non-Diabetic Patients with Invasive Breast Cancer Referring to the Cancer Institute of Iran

2021 ◽  
Author(s):  
Sanambar Sadighi ◽  
Maasoumeh Saberian ◽  
Bita Behrouzi ◽  
Massoome Najafi ◽  
Issa Jahanzad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Intervention Group ◽  
P Value ◽  
Diabetic Patients ◽  
Tumor Cell Proliferation ◽  
Breast Cancer Patients ◽  
Metformin Therapy

Background: Because of the decreasing effect of metformin on insulin resistance, it has been suggested as an anti-obesity and anti-cancer drug. So, we aimed to study the effect of metformin therapy on tumor cell proliferation in non-diabetic breast cancer patients. Methods: We conducted a prospective clinical trial and studied the effect of metformin therapy on the level of Ki67 as a measure of tumor cell proliferation. Our primary endpoint was to evaluate the changes in Ki67. The intervention group consisted of 25 non-diabetic breast cancer patients with no indication for neoadjuvant chemo- therapy. They were followed up from the time of biopsy to operation. Metformin (1500 mg/day) was prescribed in the intervention group from the date of diagnosis until the surgery (2.8 weeks). Controls were 20 early breast cancer patients who had been followed up with no prescription from biopsy until operation. Results: We could not find any statistically significant difference between the two groups regarding baseline clinical or tumor characteristics such as age, stage, grade, estrogen receptor, HER2 status or time, and type of surgery. However, the immuno- histochemistry (IHS) study showed a decrease in median Ki67 from 35.14 to 29.6 in the intervention group (P-value= 0.02). While an increase from 24.5 to 30.6 was detected in the control group (P-value= 0.02). Both of these changes were statistically significant. Although mild gastrointestinal symptoms were seen in approximately 50% of cases, generally, patients tolerated metformin well. There was a correlation between the score of HOMA, a metabolic factor, and the changes in KI67. Conclusion: Metformin prescription in a short period of time between biopsy and definitive surgery leads to the inhibition of breast cancer cell growth. We found a relationship between metformin anti-proliferative effect and glucose and insulin metabolism.

scholarly journals Targeted Inhibition of Fibroblast Growth Factor Receptor 1-GLI Through AZD4547 and GANT61 Modulates Breast Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Syeda Kiran Riaz ◽  
Walizeb Khan ◽  
Fen Wang ◽  
Tanwir Khaliq ◽  
Amber Malik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Breast Cancer Patients ◽  
Shh Pathway

The underlying mechanism of fibroblast growth factor receptor 1 (FGFR1) mediated carcinogenesis is still not fully understood. For instance, FGFR1 upregulation leads to endocrine therapy resistance in breast cancer patients. The current study aimed to identify FGFR1-linked genes to devise improved therapeutic strategies. RNA-seq and microarray expression data of 1,425 breast cancer patients from two independent cohorts were downloaded for the analysis. Gene Set Enrichment Analysis (GSEA) was performed to identify differentially expressed pathways associated with FGFR1 expression. Validation was done using 150 fresh tumor biopsy samples of breast cancer patients. The clinical relevance of mRNA and protein expression of FGFR1 and its associated genes were also evaluated in mouse embryonic fibroblasts (MEFs) and breast cancer cell line (MDA-MB-231). Furthermore, MDA-MB-231 cell line was treated with AZD4547 and GANT61 to identify the probable role of FGFR1 and its associated genes on cells motility and invasion. According to GSEA results, SHH pathway genes were significantly upregulated in FGFR1 patients in both discovery cohorts of breast cancer. Statistical analyses using both discovery cohorts and 150 fresh biopsy samples revealed strong association of FGFR1 and GLI1, a member of SHH pathway. The increase in the expression of these molecules was associated with poor prognosis, lymph node involvement, late stage, and metastasis. Combined exposures to AZD4547 (FGFR1 inhibitor) and GANT61 (GLI1 inhibitor) significantly reduced cell proliferation, cell motility, and invasion, suggesting molecular crosstalk in breast cancer progression and metastasis. A strong positive feedback mechanism between FGFR1–GLI1 axis was observed, which significantly increased cell proliferation and metastasis. Targeting FGFR1–GLI1 simultaneously will significantly improve the prognosis of breast cancer in patients.

Natural HPV58 E6 and E7 Variants Detected in Thai Breast Cancer Patients Cooperate to Induce Loss of p53 and Increase Cell Growth

2021 ◽  
Vol 104 (6) ◽  
pp. 902-910
Keyword(s):  
Breast Cancer ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Human Papillomavirus ◽  
Cell Growth ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Breast And Cervical Cancer ◽  
Cervical Cancer Cells ◽  
Hpv Oncoproteins

Background: Detection of human papillomavirus (HPV) in breast cancer patients has suggested a possible contributing role of the virus in cancer progression in this population. Objective: To investigate the presence of HPVs in Thai breast cancer patients and examine the potential activities of HPVs identified in both breast and cervical cancer cells. Materials and Methods: Fifty-five breast cancer tissues from Thai patients were subjected to HPV detection using PCR-EIA and DNA sequencing. Detection of HPV E6 proteins in sample tissues was examined by fluorescence immunohistochemistry. Cervical and two types of breast cancer cell lines expressing HPV oncogenes were established. The separate and combination of HPV oncoproteins activity for p53 degradation and specific gene regulation were investigated using western blot analysis and qPCR. Cell proliferation was assessed by MTT assay. Results: Twenty-two percent (10/45) of invasive breast cancers were found infected with various high-risk HPV types, with HPV58 E6D4G/E7T20IG63S being the most common variant. The percentage of HPV58 alone was approximately 50% (5/10) of all HPV positive samples. Similar potential oncogenic activity for this variant was observed in breast and cervical cancer cells. A separate analysis of single or combination of 58E6 (prototype or E6D4G) with 58E7 (prototype or E7T20IG63S) demonstrated that co-expression of 58E7T20IG63S with 58E6 (either prototype or E6D4G) significantly promoted cell proliferation compared to prototype 58E6/E7. Enhanced proliferation was mediated through elevated p53 degradation and reduced p21 expression. While p53 degradation activity was greatly diminished from E6 with D4G mutation, co-expression with E7T20IG63S cooperated to enhance degradation of p53 and promoted cell growth. Conclusion: HPV58 E6D4G/E7T20IG63S was the most HPV oncogene variant detected in Thai breast cancer patients. This variant exhibited in promoting cell proliferation and p53 degradation. A cooperative effect was observed in combination of HPV oncoproteins. Keywords: Human papillomavirus type 58; oncogene variant; breast cancer; Thai patients; altered cell growth

scholarly journals S100A14 serum level and its correlation with prognostic factors in breast cancer

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Noor Al-Ashkar ◽  
Almoutassem Billah Zetoune
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Control Group ◽  
Study Group ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
Cross Sectional

Abstract Background Breast cancer is the most commonly occurring cancer in women worldwide. S100A14 is a novel important member of S100 proteins family. Its importance is due to its role in tumorigenesis and metastasis process. In this study, we aimed to determine serum levels of S100A14 protein in breast cancer patients and healthy individuals to know if it can be suggested as a new biomarker for breast cancer and to reveal whether it is correlated with cancer pathological features. Methods This cross-sectional study was performed in two groups: study group contains 46 breast cancer patients (29 metastatic and 17 non-metastatic) and control group contains 22 healthy women. Enzyme-linked immunoabsorbent assay was performed to determine S100A14 protein levels in samples. Pathological data were obtained for each patient. The data were statistically analyzed using Kruskal-Wallis H, Mann-Whitney U, and Spearman correlation tests. Results S100A14 serum levels were elevated in study group compared with control group (P < 0.05). S100A14 serum levels were significantly increased in distant breast cancer patients compared with regional breast cancer patients (P = 0.001). There was a strong positive correlation between serum S100A14 level and tumor grade (rs = 0.713, P < 0.001). Conclusion Our study indicated that S100A14 serum levels are elevated in breast cancer patients compared with control individuals. High S100A14 serum levels were correlated with poor tumor differentiation so it might have a prognostic significance for breast cancer tumors. The elevation of S100A14 levels in distant breast cancer patients suggests the ability of using serum S100A14 as a biomarker for detection of breast cancer metastasis.

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