Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer

Breast Cancer Research : BCR
Aparna ShindeMichael Wendt

Abstract

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. 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 4 T1 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...Continue Reading

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Citations

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Oct 17, 2019·Antioxidants & Redox Signaling·Hai-Jian SunJin-Song Bian
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Methods Mentioned

BETA
Assay

Clinical Trials Mentioned

NCT03291938

Software Mentioned

ROUT
BreastMark
TScratch

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