Abstract A89: Glycolytic cancer cell metabolism suppressed by transplantation of exogenous normal mitochondria into human breast cancer cells

2016 ◽  
Author(s):  
Robert L. Elliott ◽  
Xian-Peng Jiang ◽  
Jonathan F. Head
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Metabolism ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Cancer Cell Metabolism

scholarly journals Prolactin Signaling Stimulates Invasion via Na+/H+ Exchanger NHE1 in T47D Human Breast Cancer Cells

2016 ◽  
Vol 30 (7) ◽  
pp. 693-708 ◽  
Author(s):  
Elena Pedraz-Cuesta ◽  
Jacob Fredsted ◽  
Helene H. Jensen ◽  
Annika Bornebusch ◽  
Lene N. Nejsum ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
T47d Cells ◽  
Nhe1 Activity

Prolactin (PRL) and its receptor (PRLR) are implicated in breast cancer invasiveness, although their exact roles remain controversial. The Na+/H+ exchanger (NHE1) plays essential roles in cancer cell motility and invasiveness, but the PRLR and NHE1 have not previously been linked. Here we show that in T47D human breast cancer cells, which express high levels of PRLR and NHE1, exposure to PRL led to the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5), Akt, and ERK1/2 signaling and the rapid formation of peripheral membrane ruffles, known to be associated with cell motility. NHE1 was present in small ruffles prior to PRL treatment and was further recruited to the larger, more dynamic ruffles induced by PRL exposure. In PRL-induced ruffles, NHE1 colocalized with activated Akt, ERK1/2, and the ERK effector p90Ribosomal S kinase (p90RSK), known regulators of NHE1 activity. Stimulation of T47D cells with PRL augmented p90RSK activation, Ser703-phosphorylation of NHE1, NHE1-dependent intracellular pH recovery, pericellular acidification, and NHE1-dependent invasiveness. NHE1 activity and localization to ruffles were attenuated by the inhibition of Akt and/or ERK1/2. In contrast, noncancerous MCF10A breast epithelial cells expressed NHE1 and PRLR at lower levels than T47D cells, and their stimulation with PRL induced neither NHE1 activation nor NHE1-dependent invasiveness. In conclusion, we show for the first time that PRLR activation stimulates breast cancer cell invasiveness via the activation of NHE1. We propose that PRL-induced NHE1 activation and the resulting NHE1-dependent invasiveness may contribute to the metastatic behavior of human breast cancer cells.

Ablation of CD44 induces glycolysis-to-oxidative phosphorylation transition via modulation of the c-Src–Akt–LKB1–AMPKα pathway

2016 ◽  
Vol 473 (19) ◽  
pp. 3013-3030 ◽  
Author(s):  
KeeSoo Nam ◽  
Sunhwa Oh ◽  
Incheol Shin
Keyword(s):  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Metabolism ◽  
Stem Cell Marker ◽  
Cancer Stem Cell Marker ◽  
Cell Marker ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Cancer Cell Metabolism

Cluster of differentiation 44 (CD44) is a transmembrane glycoprotein that has been identified as a cancer stem cell marker in various cancer cells. Although many studies have focused on CD44 as a cancer stem cell marker, its effect on cancer cell metabolism remains unclear. To investigate the role of CD44 on cancer cell metabolism, we established CD44 knock-down cells via retroviral delivery of shRNA against CD44 in human breast cancer cells. Silencing of CD44 decreased the glycolytic phenotype of cancer cells, affecting glucose uptake, ATP production, and lactate production. We also found that ablation of the CD44-induced lactate dehydrogenase (LDH) isoenzyme results in a shift to LDH1 due to LDHA down-regulation and LDHB up-regulation, implying the importance of LDH isoenzyme modulation on cancer metabolism. The expression of glycolysis-related proteins including hypoxia inducible factor-1α (HIF-1α) and LDHA was decreased by CD44 silencing. These effects were due to the up-regulation of liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)α activity by reduction in c-Src and Akt activity in CD44 knock-down cells. Finally, induction of LKB1/AMPKα activity blocked the expression of HIF-1α and its target gene, LDHA. Inversely, LDHB expression was repressed by HIF-1α. Collectively, these results indicate that the CD44 silencing-induced metabolic shift is mediated by the regulation of c-Src/Akt/LKB1/AMPKα/HIF-1α signaling in human breast cancer cells.

Upregulation of cellular triacylglycerol – free fatty acid cycling by oleate is associated with long-term serum-free survival of human breast cancer cells

2007 ◽  
Vol 85 (3) ◽  
pp. 301-310 ◽  
Author(s):  
Ewa Przybytkowski ◽  
Érik Joly ◽  
Christopher J. Nolan ◽  
Serge Hardy ◽  
Ann-Michele Francoeur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Free Survival ◽  
Serum Free

We previously showed that exogenous oleate protects human breast cancer cells against palmitate-induced apoptosis in part by increasing esterification of this free fatty acid (FFA) into triacylglycerol (TG). Here, we studied the mechanism whereby oleate protects these cells against apoptosis induced by serum withdrawal. The metabolism of FFA, TG, and glucose, in parallel with long-term cell survival in the absence of serum, was investigated in a panel of human breast cancer cell lines and in nontransformed MCF-10A cells after treatment with exogenous oleate. Short-term (3–24 h) exposure of MDA-MB-231 human breast cancer cells to exogenous oleate resulted in a dose-dependent long-term (10 day) serum-free survival that correlated with the accumulation of TG in lipid droplets and with upregulation of lipolysis. Both effects persisted for several days after oleate removal. Rapid TG lipolysis and FFA re-esterification, supported by high rates of glycolysis that provide the glycerol backbone for TG synthesis, are consistent with the presence of very active TG–FFA cycling in human breast cancer cells. Only the cancer cell lines capable of accumulating TG showed long-term serum-free survival after oleate treatment. The results suggest that upregulation of TG–FFA cycling induced by oleate may be involved in maintenance of human breast cancer cell survival.

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