De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Scaglia, Natalia; Tyekucheva, Svitlana; Zadra, Giorgia; Photopoulos, Cornelia; Loda, Massimo

doi:10.4161/cc.27767

Cited by 92 publications

(90 citation statements)

References 52 publications

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“…Interestingly, it was shown that E2F1 participates in the control of lipid synthesis concomitantly with the regulation of proliferation in cancer cells (37). This was further demonstrated by the recent finding showing that fatty acid synthesis is coordinated with cell-cycle progression in proliferating cells (38). Moreover, a biphasic model of lipid accumulation, in which cycling cells show higher levels of DNA.…”

Section: Discussionmentioning

confidence: 64%

“…Similar results were obtained in mouse models of fatty liver disease, in which E2F1 expression and activity were greatly increased, contributing to the augmentation of lipid content in the liver. Accordingly, our results showed that E2f1 dele- lipids at the G1/S and G2/M transitions, was proposed (10,38). The symmetrical effects of E2F1 on metabolic and proliferative pathways highlight the potential role of this cell-cycle regulator as a key mediator of the adapted metabolic response to proliferative stimuli, such as those observed during cancer cell transformation.…”

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis

Denechaud¹,

López-Mejía²,

Giralt³

et al. 2015

Journal of Clinical Investigation

113

112

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 83%

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis

Denechaud¹,

López-Mejía²,

Giralt³

et al. 2015

Journal of Clinical Investigation

113

112

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“…Lipid anabolism is a potentially important input into the cell cycle clock in developing myeloid cells (17). There is little known about how lipid levels are sensed by the cell cycle machinery, and it will be important to investigate this mechanism in future studies (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…E2F1 regulates the metabolic requirements of cell division by activating multiple genes involved in lipid anabolism (16). Proliferating cells increase their rate of synthesis of fatty acids during S and G 2 /M phases of the cell cycle, and this increase at G 2 /M is required for cell division (17). Therefore, E2F1 is an important determinant of cell cycle progression in mammalian cells since it coordinates lipid anabolism with the cell cycle.…”

mentioning

confidence: 99%

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism

Solomon

Podder

et al. 2017

Molecular and Cellular Biology

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During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. KEYWORDS E2F1, microRNA, PU.1, cell cycle, differentiation, lipid synthesis, myeloid cells A central problem in biology is understanding how cell division is regulated in response to developmental and environmental cues. During macrophage development, proliferating myeloid progenitor cells undergo terminal differentiation that is coordinated with reduced cell cycle progression (1). However, terminally differentiated macrophages are not necessarily permanently cell cycle arrested, as shown by evidence that epidermal Langerhans cells and brain microglia can reenter the cell cycle to self-renew (2, 3). Thus, cell cycle arrest and terminal differentiation, while normally coincident, can be independently and actively regulated. Much remains to be learned about the mechanisms by which cell-type-specific transcription factors coordinate cell cycle arrest with differentiation.

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“…Furthermore, the inhibition of fatty acid synthesis results in cell-cycle arrest at G 2 -M despite the presence of abundant fatty acids in the media. Hence, de novo lipogenesis is essential for cell-cycle completion (16). Conceivably, this "lipogenic checkpoint" at G 2 -M can be therapeutically exploited for certain hyperproliferative cancers through the use of lipogenesis inhibitors (17)(18)(19).…”

Section: Cell-cycle Checkpointsmentioning

confidence: 99%

Challenging Roadblocks to Cancer Cure

Loda

2016

Cancer Research

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The Pezcoller Symposium in Trento, Italy, June 2015, focused entirely on the question of why advanced cancer cure is so uncommon despite the extraordinarily rapid growth of invaluable therapeutic information. Participants were asked to define and to critically evaluate real and potential obstacles to permanent disease eradication. High-level concepts on potential road blocks to cures as well as opportunities for intervention in diverse areas of investigation ranging from genomic alterations to metabolism, microenvironment, immunity, and mechanotransduction were discussed. Provocative concepts and novel therapeutic avenues were proposed. What follows is a critical analysis of the highlights of this meeting. Cancer Res; 76(17); 4924-30. Ó2016 AACR.

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De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Cited by 92 publications

References 52 publications

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism

Challenging Roadblocks to Cancer Cure

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