scholarly journals Elevated Expression of DecR1 Impairs ErbB2/Neu-Induced Mammary Tumor Development

2007 ◽  
Vol 27 (18) ◽  
pp. 6361-6371 ◽  
Author(s):  
Josie Ursini-Siegel ◽  
Ashish B. Rajput ◽  
Huiling Lu ◽  
Virginie Sanguin-Gendreau ◽  
Dongmei Zuo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Fatty Acid Synthesis ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Acid Synthesis ◽  
Mammary Tumor Cells

ABSTRACT Tumor cells utilize glucose as a primary energy source and require ongoing lipid biosynthesis for growth. Expression of DecR1, an auxiliary enzyme in the fatty acid β-oxidation pathway, is significantly diminished in numerous spontaneous mammary tumor models and in primary human breast cancer. Moreover, ectopic expression of DecR1 in ErbB2/Neu-induced mammary tumor cells is sufficient to reduce levels of ErbB2/Neu expression and impair mammary tumor outgrowth. This correlates with a decreased proliferative index and reduced rates of de novo fatty acid synthesis in DecR1-expressing breast cancer cells. Although DecR1 expression does not affect glucose uptake in ErbB2/Neu-transformed cells, sustained expression of DecR1 protects mammary tumor cells from apoptotic cell death following glucose withdrawal. Moreover, expression of catalytically impaired DecR1 mutants in Neu-transformed breast cancer cells restored Neu expression levels and increased mammary tumorigenesis in vivo. These results argue that DecR1 is sufficient to limit breast cancer cell proliferation through its ability to limit the extent of oncogene expression and reduce steady-state levels of de novo fatty acid synthesis. Furthermore, DecR1-mediated suppression of tumorigenesis can be uncoupled from its effects on Neu expression. Thus, while downregulation of Neu expression may contribute to DecR1-mediated tumor suppression in certain cell types, this is not an obligate event in all Neu-transformed breast cancer cells.

The impact of medicinal plant Ocimum minimum L. on fatty acid synthesis process in breast cancer cells

Biologia ◽  
2022 ◽  
Author(s):  
Jovana V. Jovankić ◽  
Danijela M. Cvetković ◽  
Milena G. Milutinović ◽  
Danijela D. Nikodijević ◽  
Aleksandra G. Nikezić ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Breast Cancer Cells ◽  
Acid Synthesis ◽  
Synthesis Process ◽  
The Impact

scholarly journals [Corrigendum] A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

2020 ◽  
Author(s):  
Alejandro Schcolnik‑Cabrera ◽  
Guadalupe Dominguez‑G�mez ◽  
Alma Ch�vez‑Blanco ◽  
Marisol Ram�rez‑Yautentzi ◽  
Roc�o Morales‑B�rcenas ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Human Colon ◽  
Acid Synthesis ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression

2021 ◽  
Vol 118 (34) ◽  
pp. e2020227118
Author(s):  
David Buechel ◽  
Nami Sugiyama ◽  
Natalia Rubinstein ◽  
Meera Saxena ◽  
Ravi K. R. Kalathur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Wnt Signaling ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Dual Function ◽  
Mammary Tumor Cells ◽  
Cell Cell

During malignant progression, epithelial cancer cells dissolve their cell–cell adhesion and gain invasive features. By virtue of its dual function, β-catenin contributes to cadherin-mediated cell–cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bcl9 and Pygopus, and via the C terminus, it interacts with the general transcriptional machinery. This duality confounds the simple loss-of-function analysis of Wnt signaling in cancer progression. In many cancer types including breast cancer, the functional contribution of β-catenin’s transcriptional activities, as compared to its adhesion functions, to tumor progression has remained elusive. Employing the mouse mammary tumor virus (MMTV)–PyMT mouse model of metastatic breast cancer, we compared the complete elimination of β-catenin with the specific ablation of its signaling outputs in mammary tumor cells. Notably, the complete lack of β-catenin resulted in massive apoptosis of mammary tumor cells. In contrast, the loss of β-catenin’s transcriptional activity resulted in a reduction of primary tumor growth, tumor invasion, and metastasis formation in vivo. These phenotypic changes were reflected by stalled cell cycle progression and diminished epithelial–mesenchymal transition (EMT) and cell migration of breast cancer cells in vitro. Transcriptome analysis revealed subsets of genes which were specifically regulated by β-catenin’s transcriptional activities upon stimulation with Wnt3a or during TGF-β–induced EMT. Our results uncouple the signaling from the adhesion function of β-catenin and underline the importance of Wnt/β-catenin–dependent transcription in malignant tumor progression of breast cancer.

scholarly journals HEYL Regulates Neoangiogenesis Through Overexpression in Both Breast Tumor Epithelium and Endothelium

2021 ◽  
Vol 10 ◽  
Author(s):  
Liangfeng Han ◽  
Preethi Korangath ◽  
Nguyen K. Nguyen ◽  
Adam Diehl ◽  
Soonweng Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Downstream Target ◽  
Mammary Tumor Cells

Blocking tumor angiogenesis is an appealing therapeutic strategy, but to date, success has been elusive. We previously identified HEYL, a downstream target of Notch signaling, as an overexpressed gene in both breast cancer cells and as a tumor endothelial marker, suggesting that HEYL overexpression in both compartments may contribute to neoangiogenesis. Carcinomas arising in double transgenic Her2-neu/HeyL mice showed higher tumor vessel density and significantly faster growth than tumors in parental Her2/neu mice. Providing mechanistic insight, microarray-based mRNA profiling of HS578T-tet-off-HEYL human breast cancer cells revealed upregulation of several angiogenic factors including CXCL1/2/3 upon HEYL expression, which was validated by RT-qPCR and protein array analysis. Upregulation of the cytokines CXCL1/2/3 occurred through direct binding of HEYL to their promoter sequences. We found that vessel growth and migration of human vascular endothelial cells (HUVECs) was promoted by conditioned medium from HS578T-tet-off-HEYL carcinoma cells, but was blocked by neutralizing antibodies against CXCL1/2/3. Supporting these findings, suppressing HEYL expression using shRNA in MDA-MB-231 cells significantly reduced tumor growth. In addition, suppressing the action of proangiogenic cytokines induced by HEYL using a small molecule inhibitor of the CXCl1/2/3 receptor, CXCR2, in combination with the anti-VEGF monoclonal antibody, bevacizumab, significantly reduced tumor growth of MDA-MB-231 xenografts. Thus, HEYL expression in tumor epithelium has a profound effect on the vascular microenvironment in promoting neoangiogenesis. Furthermore, we show that lack of HEYL expression in endothelial cells leads to defects in neoangiogenesis, both under normal physiological conditions and in cancer. Thus, HeyL-/- mice showed impaired vessel outgrowth in the neonatal retina, while the growth of mammary tumor cells E0771 was retarded in syngeneic HeyL-/- mice compared to wild type C57/Bl6 mice. Blocking HEYL’s angiogenesis-promoting function in both tumor cells and tumor-associated endothelium may enhance efficacy of therapy targeting the tumor vasculature in breast cancer.

Metabolic Remodeling Induced by Adipocytes: A New Achilles' Heel in Invasive Breast Cancer?

2020 ◽  
Vol 27 (24) ◽  
pp. 3984-4001 ◽  
Author(s):  
Camille Attané ◽  
Delphine Milhas ◽  
Andrew J. Hoy ◽  
Catherine Muller
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Fatty Acid Oxidation ◽  
De Novo ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Oxidation Inhibitors ◽  
Metabolic Remodeling

Metabolic reprogramming represents an important hallmark of cancer cells. Besides de novo fatty acid synthesis, it is now clear that cancer cells can acquire Fatty Acids (FA) from tumor-surrounding adipocytes to increase their invasive capacities. Indeed, adipocytes release FA in response to tumor secreted factors that are transferred to tumor cells to be either stored as triglycerides and other complex lipids or oxidized in mitochondria. Like all cells, FA can be released over time from triglyceride stores through lipolysis and then oxidized in mitochondria in cancer cells. This metabolic interaction results in specific metabolic remodeling in cancer cells, and underpins adipocyte stimulated tumor progression. Lipolysis and fatty acid oxidation therefore represent novel targets of interest in the treatment of cancer. In this review, we summarize the recent advances in our understanding of the metabolic reprogramming induced by adipocytes, with a focus on breast cancer. Then, we recapitulate recent reports studying the effect of lipolysis and fatty acid oxidation inhibitors on tumor cells and discuss the interest to target these metabolic pathways as new therapeutic approaches for cancer.

scholarly journals Fatty Acid Synthesis and Degradation Interplay to Regulate the Oxidative Stress in Cancer Cells

2019 ◽  
Vol 20 (6) ◽  
pp. 1348 ◽  
Author(s):  
Valeryia Mikalayeva ◽  
Ieva Ceslevičienė ◽  
Ieva Sarapinienė ◽  
Vaidotas Žvikas ◽  
Vytenis Skeberdis ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Breast Cancer Cells ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Synthesis And Degradation

Both cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) have been shown to play a role in the survival and proliferation of cancer cells. This study aimed to confirm experimentally whether FAS and FAO coexist in breast cancer cells (BCC). By feeding cells with 13C-labeled glutamine and measuring labeling patterns of TCA intermediates, it was possible to show that part of the cytosolic acetyl-CoA used in lipid synthesis is also fed back into the mitochondrion via fatty acid degradation. This results in the transfer of reductive potential from the cytosol (in the form of NADPH) to the mitochondrion (in the form of NADH and FADH2). The hypothesized mechanism was further confirmed by blocking FAS and FAO with siRNAs. Exposure to staurosporine (which induces ROS production) resulted in the disruption of simultaneous FAS and FAO, which could be explained by NADPH depletion.

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