scholarly journals Aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector, fuels breast cancer cell proliferation

2020 ◽  
Author(s):  
Valeria Canu ◽  
Sara Donzelli ◽  
Andrea Sacconi ◽  
Federica Lo Sardo ◽  
Claudio Pulito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Disease Free Survival ◽  
High Expression ◽  
Hippo Signaling ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
And Migration

AbstractSperm-associated antigen 5 (SPAG5) is an important driver of the cell mitotic spindle required for chromosome segregation and progression into anaphase. SPAG5 has been identified as an important proliferation marker and chemotherapy-sensitivity predictor, especially in estrogen receptor-negative breast cancer subtypes. Here, we report that SPAG5 is a direct target of miR-10b-3p, and its aberrantly high expression associates with poor disease-free survival in two large cohorts of breast cancer patients. SPAG5 depletion strongly impaired cancer cell cycle progression, proliferation, and migration. Interestingly, high expression of SPAG5 pairs with a YAP/TAZ-activated signature in breast cancer patients. Reassuringly, the depletion of YAP, TAZ, and TEAD strongly reduced SPAG5 expression and diminished its oncogenic effects. YAP, TAZ coactivators, and TEAD transcription factors are key components of the Hippo signaling pathway involved in tumor initiation, progression, and metastasis. Furthermore, we report that SPAG5 is a direct transcriptional target of TEAD/YAP/TAZ, and pharmacological targeting of YAP and TAZ severely reduces SPAG5 expression. Collectively, our data uncover an oncogenic feedback loop, comprising miR-10b-3p, SPAG5, and YAP/TAZ/TEAD, which fuels the aberrant proliferation of breast cancer.

scholarly journals PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2742
Author(s):  
Ramona Erber ◽  
Julia Meyer ◽  
Helge Taubert ◽  
Peter A. Fasching ◽  
Sven Wach ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Subtypes ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Cancer Subtypes ◽  
Prognostic Effect ◽  
Enhanced Expression ◽  
Disease Free

PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.

scholarly journals MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5382
Author(s):  
Pei-Yi Chu ◽  
Hsing-Ju Wu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Protein Expression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Expression Ratio

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

scholarly journals Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Subtypes ◽  
Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

scholarly journals Serum N-glycan profiles differ for various breast cancer subtypes

2021 ◽  
Author(s):  
Gerda C. M. Vreeker ◽  
Kiki M. H. Vangangelt ◽  
Marco R. Bladergroen ◽  
Simone Nicolardi ◽  
Wilma E. Mesker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Cancer Patients ◽  
High Resolution Mass Spectrometry ◽  
Case Control ◽  
Total Serum ◽  
Screening Methods ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Control Comparison

AbstractBreast cancer is the most prevalent cancer in women. Early detection of this disease improves survival and therefore population screenings, based on mammography, are performed. However, the sensitivity of this screening modality is not optimal and new screening methods, such as blood tests, are being explored. Most of the analyses that aim for early detection focus on proteins in the bloodstream. In this study, the biomarker potential of total serum N-glycosylation analysis was explored with regard to detection of breast cancer. In an age-matched case-control setup serum protein N-glycan profiles from 145 breast cancer patients were compared to those from 171 healthy individuals. N-glycans were enzymatically released, chemically derivatized to preserve linkage-specificity of sialic acids and characterized by high resolution mass spectrometry. Logistic regression analysis was used to evaluate associations of specific N-glycan structures as well as N-glycosylation traits with breast cancer. In a case-control comparison three associations were found, namely a lower level of a two triantennary glycans and a higher level of one tetraantennary glycan in cancer patients. Of note, various other N-glycomic signatures that had previously been reported were not replicated in the current cohort. It was further evaluated whether the lack of replication of breast cancer N-glycomic signatures could be partly explained by the heterogenous character of the disease since the studies performed so far were based on cohorts that included diverging subtypes in different numbers. It was found that serum N-glycan profiles differed for the various cancer subtypes that were analyzed in this study.

Breast Cancer in the Elderly

2007 ◽  
Vol 25 (14) ◽  
pp. 1882-1890 ◽  
Author(s):  
Diana Crivellari ◽  
Matti Aapro ◽  
Robert Leonard ◽  
Gunter von Minckwitz ◽  
Etienne Brain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Life Expectancy ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Cost Benefit ◽  
The Elderly ◽  
Breast Cancer Patients ◽  
Younger Women ◽  
Based Medicine

Screening and adjuvant postoperative therapies have increased survival among women with breast cancer. These tools are seldom applied in elderly patients, although the usually reported incidence of breast cancer is close to 50% in women 65 years or older, reaching 47% after 70 years in the updated Surveillance, Epidemiology, and End Results (SEER) database. Elderly breast cancer patients, even if in good medical health, were frequently excluded from adjuvant clinical trials. Women age 70 years who are fit actually have a median life expectancy of 15.5 years, ie, half of them will live much longer and will remain exposed for enough time to the potentially preventable risks of a relapse and specific death. In the last few years, a new concern about this issue has developed. Treatment now faces two major end points, as in younger women: to improve disease-free survival in the early stages, and to palliate symptoms in advanced disease. However, in both settings, the absolute benefit of treatment is critical because protecting quality of life and all its related aspects (especially functional status and independence), is crucial in older persons who have more limited life expectancy. Furthermore, the new hormonal compounds (aromatase inhibitors) and chemotherapeutic drugs (capecitabine, liposomal doxorubicin), are potentially less toxic than and equally as effective as older more established therapies. These new treatments bring new challenges including higher cost, and defining their benefit in elderly breast cancer must include an analysis of the cost/benefit ratio. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients both in the adjuvant and metastatic settings, a move that will take us from a prejudiced, age-based medicine to an evidence-based medicine.

Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

2020 ◽  
Vol 33 (4) ◽  
pp. 137-144
Author(s):  
Guillermo Peralta-Castillo ◽  
Antonio Maffuz-Aziz ◽  
Mariana Sierra-Murguía ◽  
Sergio Rodriguez-Cuevas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free
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