Increased lipogenesis in cancer cells: new players, novel targets

Swinnen, Johannes V.; Brusselmans, Koen; Verhoeven, Guido

doi:10.1097/01.mco.0000232894.28674.30

Cited by 544 publications

(452 citation statements)

References 78 publications

(85 reference statements)

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“…Activation of de novo lipogenesis is found in many types of malignancy, including HCC (Bhalla et al ., 2012; Jacobs et al ., 2012; Liu et al ., 2016; Rysman et al ., 2010). In cancer cells, unrestricted lipogenesis is essential for the continued supply of lipids and lipid precursors to maintain membrane production, synthesis of signal transducers, and post‐translational modification of proteins (Menendez and Lupu, 2007; Swinnen et al ., 2006). Since hepatocytes are mainly responsible for lipid synthesis and storage, lipid metabolism plays a more important role in the development of liver cancer.…”

Section: Introductionmentioning

confidence: 99%

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

et al. 2018

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Although identified as a growth factor, the mechanism by which hepatoma‐derived growth factor (HDGF) promotes cancer development remains unclear. We found that nuclear but not cytoplasmic HDGF is closely associated with prognosis of hepatocellular carcinoma (HCC). RNA‐sequencing analysis further demonstrated that the nuclear role of HDGF involved regulation of transcription of lipid metabolism genes. HDGF‐induced expression of lipogenic genes was mainly associated with activation of sterol regulatory element binding protein (SREBP) transcription factor. Coexpression of SREBP‐1 and nuclear HDGF predicts poor prognosis for HCC. In addition, by changing the first amino acid of the PWWP domain from proline to alanine, the type of PWWP domain changed from P‐ to A‐type, resulting in inability to induce SREBP‐1‐mediated gene transcription. The type of PWWP domain affects the recruitment of the C‐terminal binding protein‐1 transcriptional repressor on the promoter of the lipogenic gene. Our data indicate that HDGF acts as a coactivator of SREBP1‐mediated transcription of lipogenic genes. The PWWP domain is crucial for HDGF to promote lipogenesis. Moreover, transcriptional regulation of nuclear HDGF plays important roles in the development of HCC.

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Section: Introductionmentioning

confidence: 99%

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

et al. 2018

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“…From a metabolic point of view, cell cycle progression is an energy-demanding process that can be executed only if cells have sufficient metabolic resources to support doubling of cell mass. 6 It is well-known that high energetic requirements of tumors are mainly satisfied by enhanced glycolytic rate, 7,8 whereas biosynthetic needs to support the high proliferation rate are provided by enhanced lipogenesis 9 and nucleotide synthesis. 10,11 The pentose phosphate pathway (PPP), which was described as a cycle in 1955, 12,13 produces ribose-5-phosphate that may be used for the synthesis of nucleotides.…”

mentioning

confidence: 99%

Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29

Vizán

Alcarraz-Vizán

Díaz-Moralli

et al. 2009

Intl Journal of Cancer

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Cell cycle regulation is dependent on multiple cellular and molecular events. Cell proliferation requires metabolic sources for the duplication of DNA and cell size. However, nucleotide reservoirs are not sufficient to support cell duplication and, therefore, biosynthetic pathways should be upregulated during cell cycle. Here, we reveal that glucose-6-phosphate dehydrogenase (G6PDH) and transketolase (TKT), the 2 key enzymes of oxidative and nonoxidative branches of the pentose phosphate pathway (PPP), respectively, which is necessary for nucleotide synthesis, are enhanced during cell cycle progression of the human colon cancer cell line HT29. These enhanced enzyme activities coincide with an increased ratio of pentose monophosphate to hexose monophosphate pool during late G1 and S phase, suggesting a potential role for pentose phosphates in proliferating signaling. Isotopomeric analysis distribution of nucleotide ribose synthesized from 1,2-13 C 2 -glucose confirms the activation of the PPP during late G1 and S phase and reveals specific upregulation of the oxidative branch. Our data sustain the idea of a critical oxidative and nonoxidative balance in cancer cells, which is consistent with a late G1 metabolic check point. The distinctive modulation of these enzymes during cell cycle progression may represent a new strategy to inhibit proliferation in anticancer treatments. ' 2009 UICC

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“…In several solid tumors, including breast, prostate, lung, and colon carcinomas, cancer cells, due to their high requirement in energy and cell membrane, synthesize high amount of fatty acids (FA) via an increased expression and activity of lipogenic enzymes [3][4][5]. Figure 1 shows schematically the pathways leading to energy production and lipid synthesis in cancer cells.…”

Section: Increased In Situ Lipogenesis In Cancer Cells Compared To Nomentioning

confidence: 99%

“…The in situ biosynthesis of palmitic acid from citrate was demonstrated by different groups to be increased by sex steroid hormones in breast and prostate cancers for the synthesis of membrane and signaling phospholipids. Three enzymes involved in the synthesis of long-chain FA are overexpressed in breast and prostate cancers [3]. They are ATP citrate lyase, acetyl-CoA carboxylase (ACC1/2), a rate-limiting enzyme which generates malonyl CoA, and fatty acid synthase (FASN), the key multifunctional enzyme catalyzing the synthesis of long-chain FA from the condensation of acetyl CoA with malonyl CoA [7].…”

Section: Increased In Situ Lipogenesis In Cancer Cells Compared To Nomentioning

confidence: 99%

The Role of Sex Steroid Receptors on Lipogenesis in Breast and Prostate Carcinogenesis: A Viewpoint

Rochefort

Chalbos

2010

HORM CANC

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Cancer cells require both nutrients and mitogens to multiply and survive in the unfavorable microenvironment of solid tumors or metastases before angiogenesis. Most cancer cells do not use fatty acids (FA) from the circulation but synthesize them in situ especially to make membranes and lipid signals required for continuously dividing cells. Three lipogenic enzymes are overexpressed, induced by sex steroid hormones and responsible for the in situ increased lipogenesis in cancer cells. We propose that in the early stages of human breast and prostate carcinogenesis, an increased activity of sex steroid receptors is partly responsible for the overexpression of FA synthase (FASN) whose regulation in cancer cells has been particularly studied. Increased activity of androgen receptor (AR), via different mechanisms, was extensively reported in prostate cancer. An increased level/and or activity of progesterone receptors, correlated with an increased expression of FASN, was found both in early stages of breast carcinogenesis and during the hormone replacement therapy of menopausal women. While the majority of recent targeted therapies are based on inhibition of mitogenic pathways, the inhibition of cancer cell nutrition by interfering with lipid synthesis and hormone action should open the way to new therapeutic and preventive approaches of hormonedependent cancers.

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Increased lipogenesis in cancer cells: new players, novel targets

Cited by 544 publications

References 78 publications

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29

The Role of Sex Steroid Receptors on Lipogenesis in Breast and Prostate Carcinogenesis: A Viewpoint

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