Loss of FBP1 by Snail-Mediated Repression Provides Metabolic Advantages in Basal-like Breast Cancer

Dong, Chenfang; Yuan, Tingting; Wu, Yadi; Wang, Yifan; Fan, Teresa W.‐M.; Miriyala, Sumitra; Lin, Yiwei; Yao, Jun; Shi, Jian; Kang, Tiebang; Lorkiewicz, Pawel; Clair, Daret St.; Hung, Mien‐Chie; Evers, B. Mark; Zhou, Binhua P.

doi:10.1016/j.ccr.2013.01.022

Cited by 656 publications

(699 citation statements)

References 39 publications

(45 reference statements)

Supporting

Mentioning

661

Contrasting

Unclassified

Order By: Relevance

“…Snail-mediated metabolic regulation of EMT may be another important reason for the acquisition of CSC properties in breast cancer. Our study found that ectopic FBP1 expression inhibited morphological changes indicative of EMT, indicating the importance of FBP1 for this event (Dong et al, 2013b). These findings are in line with the notion that expression of FBP1 suppresses CSC phenotypes and tumorigenicity.…”

Section: Metabolic Reprogramming In Breast Cscssupporting

confidence: 80%

“…These intriguing findings indicate that the selfrenewal potential of CSCs in different tissues may be sensitive to levels of ROS, and that the glycolytic switch reduces ROS and facilitates the maintenance of the pluripotent state in CSCs. In our study, loss of FBP1 by Snail-mediated repression could decrease mitochondrial ROS by increasing aerobic glycolysis and suppressing oxygen consumption (Dong et al, 2013b). ROS can mediate the regulation of the Wnt pathway.…”

Section: Metabolic Reprogramming In Breast Cscsmentioning

confidence: 91%

“…These findings suggest that the process of reprogramming is associated with a major bioenergetic restructuring to facilitate a conversion from somatic mitochondrial oxidation to a glycolysis-dependent pluripotent state. Our recent study has shown that metabolic reprogramming contributes to the acquisition of CSC properties in breast cancer cells (Dong et al, 2013b). Loss of fructose-1,6-bisphosphatase (FBP1), a rate-limiting enzyme in gluconeogenesis, which catalyzes the splitting of fructose-1,6-bisphosphate (F-1,6-BP) into fructose 6-phosphate and inorganic phosphate, results in a metabolic switch from OXPHOS to aerobic glycolysis in breast cancer cells.…”

Section: Metabolic Reprogramming In Breast Cscsmentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic and metabolic regulation of breast cancer stem cells

Liu

Dong

2015

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Abstract:Breast cancer has a relatively high mortality rate in women due to recurrence and metastasis. Increasing evidence has identified a rare population of cells with stem cell-like properties in breast cancer. These cells, termed cancer stem cells (CSCs), which have the capacity for self-renewal and differentiation, contribute significantly to tumor progression, recurrence, drug resistance and metastasis. Clarifying the mechanisms regulating breast CSCs has important implications for our understanding of breast cancer progression and therapeutics. A strong connection has been found between breast CSCs and epithelial mesenchymal transition (EMT). In addition, recent studies suggest that the maintenance of the breast CSC phenotype is associated with epigenetic and metabolic regulation. In this review, we focus on recent discoveries about the connection between EMT and CSC, and advances made in understanding the roles and mechanisms of epigenetic and metabolic reprogramming in controlling breast CSC properties.

show abstract

Section: Metabolic Reprogramming In Breast Cscssupporting

confidence: 80%

Section: Metabolic Reprogramming In Breast Cscsmentioning

confidence: 91%

Section: Metabolic Reprogramming In Breast Cscsmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic and metabolic regulation of breast cancer stem cells

Liu

Dong

2015

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

show abstract

“…Consistent with these observations, some cancer cells undergo metabolic changes during invasion in vitro and metastasis in vivo that would be expected to reduce the generation of ROS (Chen et al 2007;Lu et al 2010;Qu et al 2011;Kamarajugadda et al 2012Kamarajugadda et al , 2013Dong et al 2013;Shi et al 2014). For example, HIF-1 activity is transiently increased during metastasis due to high ROS levels (Montagner et al 2012;Zhao et al 2014).…”

Section: Cancer Cells Undergo Metabolic Changes To Manage Rossupporting

confidence: 54%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

207

141

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are highly reactive molecules that arise from a number of cellular sources, including oxidative metabolism in mitochondria. At low levels they can be advantageous to cells, activating signaling pathways that promote proliferation or survival. At higher levels, ROS can damage or kill cells by oxidizing proteins, lipids, and nucleic acids. It was hypothesized that antioxidants might benefit high-risk patients by reducing the rate of ROS-induced mutations and delaying cancer initiation. However, dietary supplementation with antioxidants has generally proven ineffective or detrimental in clinical trials. High ROS levels limit cancer cell survival during certain windows of cancer initiation and progression. During these periods, dietary supplementation with antioxidants may promote cancer cell survival and cancer progression. This raises the possibility that rather than treating cancer patients with antioxidants, they should be treated with pro-oxidants that exacerbate oxidative stress or block metabolic adaptations that confer oxidative stress resistance.

show abstract

“…Reduction in SirT3 levels and the resulting elevated ROS levels have been directly linked to the switch to glycolysis, known as the Warburg effect (8). While ROS are required for glucose metabolism and metastasis in triple-negative breast cancers (9), decreased SirT3 levels concomitant with high ROS levels are frequently observed in all breast cancers (8). Based on these findings, SirT3 is considered a tumor suppressor (5,8).…”

mentioning

confidence: 99%

SirT3 Regulates the Mitochondrial Unfolded Protein Response

Papa

Germain

2014

Molecular and Cellular Biology

226

200

View full text Add to dashboard Cite

The mitochondria of cancer cells are characterized by elevated oxidative stress caused by reactive oxygen species (ROS). Such an elevation in ROS levels contributes to mitochondrial reprogramming and malignant transformation. However, high levels of ROS can cause irreversible damage to proteins, leading to their misfolding, mitochondrial stress, and ultimately cell death. Therefore, mechanisms to overcome mitochondrial stress are needed. The unfolded protein response (UPR) triggered by accumulation of misfolded proteins in the mitochondria (UPR mt ) has been reported recently. So far, the UPR mt has been reported to involve the activation of CHOP and estrogen receptor alpha (ER␣). The current study describes a novel role of the mitochondrial deacetylase SirT3 in the UPR mt . Our data reveal that SirT3 acts to orchestrate two pathways, the antioxidant machinery and mitophagy. Inhibition of SirT3 in cells undergoing proteotoxic stress severely impairs the mitochondrial network and results in cellular death. These observations suggest that SirT3 acts to sort moderately stressed from irreversibly damaged organelles. Since SirT3 is reported to act as a tumor suppressor during transformation, our findings reveal a dual role of SirT3. This novel role of SirT3 in established tumors represents an essential mechanism of adaptation of cancer cells to proteotoxic and mitochondrial stress. Mitochondrial reprogramming associated with elevated reactive oxygen species (ROS) levels is a hallmark of cancers. Altered mitochondrial metabolism and ROS, both required during oncogenic transformation (1-4), are regulated by the mitochondrial deacetylase SirT3 (5-7). Reduction in SirT3 levels and the resulting elevated ROS levels have been directly linked to the switch to glycolysis, known as the Warburg effect (8). While ROS are required for glucose metabolism and metastasis in triple-negative breast cancers (9), decreased SirT3 levels concomitant with high ROS levels are frequently observed in all breast cancers (8). Based on these findings, SirT3 is considered a tumor suppressor (5,8).SirT3 regulates the activity of magnesium superoxide dismutase (MnSOD), which detoxifies superoxide to hydrogen peroxide (5,7,(10)(11)(12)(13)(14). Moreover, SirT3 has been linked to augmented transcription of MnSOD and catalase, both known targets of the transcription factor FOXO3A (15). The SirT3-dependent deacetylation of FOXO3A promotes both its nuclear translocation and its transcriptional activity (16,17). Therefore, mechanistically, the reduction of SirT3 levels leads to an elevation in ROS levels by compromising the mitochondrial antioxidant machinery.Mitochondria are the main source of ROS production (18). However, they are also the main targets of oxidative stress. Excessive ROS induce oxidative damage to DNA, lipids, and proteins, leading to their misfolding and aggregation in the mitochondria. Upon accumulation of misfolded and aggregated proteins in the mitochondria, cells mount the unfolded protein response (UPR mt ), a mitochondrial-to nu...

show abstract

Loss of FBP1 by Snail-Mediated Repression Provides Metabolic Advantages in Basal-like Breast Cancer

Cited by 656 publications

References 39 publications

Epigenetic and metabolic regulation of breast cancer stem cells

Epigenetic and metabolic regulation of breast cancer stem cells

Cancer, Oxidative Stress, and Metastasis

SirT3 Regulates the Mitochondrial Unfolded Protein Response

Contact Info

Product

Resources

About