scholarly journals Inhibition of pyruvate carboxylase by 1α,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression

2017 ◽  
Vol 411 ◽  
pp. 171-181 ◽  
Author(s):  
Tomasz Wilmanski ◽  
Xuanzhu Zhou ◽  
Wei Zheng ◽  
Aparna Shinde ◽  
Shawn S. Donkin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Early Breast Cancer ◽  
Cancer Progression ◽  
Pyruvate Carboxylase ◽  
Breast Cancer Progression ◽  
Dihydroxyvitamin D

scholarly journals Targeting Pyruvate Carboxylase by a Small Molecule Suppresses Breast Cancer Progression

2020 ◽  
Vol 7 (9) ◽  
pp. 1903483
Author(s):  
Qingxiang Lin ◽  
Yuan He ◽  
Xue Wang ◽  
Yong Zhang ◽  
Meichun Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Small Molecule ◽  
Pyruvate Carboxylase ◽  
Breast Cancer Progression

scholarly journals Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer

2018 ◽  
Author(s):  
Aparna Shinde ◽  
Tomasz Wilmanski ◽  
Hao Chen ◽  
Dorothy Teegarden ◽  
Michael K. Wendt
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Copy Number ◽  
Pyruvate Carboxylase ◽  
Patient Survival ◽  
Metastatic Breast

AbstractBackground: Overcoming systemic dormancy and initiating secondary tumor grow under unique microenvironmental conditions is a major rate-limiting step in metastatic progression. Disseminated tumor cells encounter major changes in nutrient supplies and oxidative stresses compared to the primary tumor and must demonstrate significant metabolic plasticity to adapt to specific metastatic sites. Recent studies suggest that differential utilization of pyruvate sits as a critical node in determining the organotropism of metastatic breast cancer. Pyruvate carboxylase (PC) is key enzyme that converts pyruvate into oxaloacetate for utilization in gluconeogenesis and replenishment of the TCA cycle.Methods: Patient survival was analyzed with respect to gene copy number alterations and differential mRNA expression levels of PC. Expression of PC was analyzed in the MCF-10A, D2-HAN and the 4T1 breast cancer progression series under in vitro and in vivo growth conditions. PC expression was depleted via shRNAs and the impact on in vitro cell growth, mammary fat pad tumor growth, and pulmonary and non-pulmonary metastasis was assessed by bioluminescent imaging. Changes in glycolytic capacity, oxygen consumption and response to oxidative stress were quantified upon PC depletion.Results: Genomic copy number increases in PC were observed in 16-30% of metastatic breast cancer patients. High expression of PC mRNA was associated with decreased patient survival in the MCTI and METABRIC patient datasets. Enhanced expression of PC was not recapitulated in breast cancer progression models when analyzed under glucose-rich in vitro culture conditions. In contrast, PC expression was dramatically enhanced upon glucose deprivation and in vivo in pulmonary metastases. Depletion of PC led to a dramatic decrease in 4T1 pulmonary metastasis but did not affect orthotopic primary tumor growth. Tail vein inoculations confirmed the role of PC in facilitating pulmonary, but not extra-pulmonary tumor initiation. PC-depleted cells demonstrated a decrease in glycolytic capacity and oxygen consumption rates and an enhanced sensitivity to oxidative stress.Conclusions: Our studies indicate that PC is specifically required for the growth of breast cancer that has disseminated to the lungs. Overall, these findings point to the potential of targeting PC for the treatment of pulmonary metastatic breast cancer.

scholarly journals Long noncoding RNA BHLHE40‐AS1 promotes early breast cancer progression through modulating IL‐6/STAT3 signaling

2020 ◽  
Vol 121 (7) ◽  
pp. 3465-3478 ◽  
Author(s):  
Rebecca S. DeVaux ◽  
Ali S. Ropri ◽  
Sandra L. Grimm ◽  
Peter A. Hall ◽  
Emilio O. Herrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Progression ◽  
Stat3 Signaling

Beta haemoglobin (hbb) is a novel marker of breast cancer progression

2014 ◽  
Author(s):  
Mattia Capulli ◽  
Adriano Angelucci ◽  
Anna Teti ◽  
Patrizia Sanita ◽  
Luca Ventura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Breast Cancer Progression
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