Cholesterol metabolism and colorectal cancers

Jacobs, Rutger J.; Voorneveld, Philip W.; Kodach, Liudmila L.; Hardwick, James C.H.

doi:10.1016/j.coph.2012.07.010

Cited by 48 publications

(42 citation statements)

References 52 publications

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“…Early epidemiological studies have reported an inverse association between serum total cholesterol and CRC risk,29 30 whereas recent prospective studies have found no associations or an increased risk with higher serum total cholesterol levels 5 12 14 31. A possible explanation for these contradictory findings can be due to the fact that various studies have not taken into account the effect of reverse causation: undiagnosed cancer can have metabolic effects on serum total cholesterol levels, leading to lower serum total cholesterol levels 8. In our study, to reduce the potential of reverse causations, we excluded first 2 years of CRC cases.…”

Section: Discussionmentioning

confidence: 99%

“…Cholesterol plays a role in the formation of lipid rafts, which can serve as privileged sites for cell signalling, apoptosis, migration and invasion in human cancer development 32 33. Another mechanism linking cholesterol with CRC is its role on inflammatory pathways that affect proliferation and apoptosis of cancer cells 8 34. Finally, cholesterol is also the precursor of bile acids and the polymorphisms of the enzyme involved in this metabolic pathway have been shown to be associated with CRC risk, although the results have been not consistent 8 35…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it may be plausible that PUFAs interact with cholesterol in tumourgenesis. On the other hand, PUFAs may inhibit inflammation by altering fatty acid composition of cell membranes and may, thereby, counteract the effect of cholesterol on inflammatory responses, promoting proliferation and apoptosis of cells in CRC 8 19. However, the interaction between dietary PUFAs intake and serum total cholesterol on CRC risk is still an understudied area in population-based settings.…”

Section: Introductionmentioning

confidence: 99%

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Dietary polyunsaturated fatty acids intake modifies the positive association between serum total cholesterol and colorectal cancer risk: the Rotterdam Study

Muka¹,

Kraja

Ruiter

et al. 2016

J Epidemiol Community Health

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dietary polyunsaturated fatty acids intake modifies the positive association between serum total cholesterol and colorectal cancer risk: the Rotterdam Study

Muka¹,

Kraja

Ruiter

et al. 2016

J Epidemiol Community Health

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“…Metabolic disorders have been identified as a hallmark of cancer (Hanahan and Weinberg, 2011). 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).…”

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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“…De novo lipogenesis is highly activated in many types of malignant tumors, resulting in intracellular unusual lipids accumulation, which is involved in tumor progression (1)(2)(3). In contrast to normal cells, in malignant tumors, lipids are mainly derived from new synthesis instead of extracellular lipids uptake.…”

Section: Introductionmentioning

confidence: 99%

Arginine Methylation of SREBP1a via PRMT5 Promotes De Novo Lipogenesis and Tumor Growth

Liu

Zhao

et al. 2016

Cancer Research

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Dysregulation of the sterol regulatory element-binding transcription factors sterol regulatory element-binding protein (SREBP) and SREBF activates de novo lipogenesis to high levels in cancer cells, a critical event in driving malignant growth. In this study, we identified an important posttranslational mechanism by which SREBP1a is regulated during metabolic reprogramming in cancer cells. Mass spectrometry revealed protein arginine methyltransferase 5 (PRMT5) as a binding partner of SREBP1a that symmetrically dimethylated it on R321, thereby promoting transcriptional activity. Furthermore, PRMT5-induced methylation prevented phosphorylation of SREBP1a on S430 by GSK3b, leading to its disassociation from Fbw7 (FBXW7) and its evasion from degradation through the ubiquitin-proteasome pathway. Consequently, methylation-stabilized SREBP1a increased de novo lipogenesis and accelerated the growth of cancer cells in vivo and in vitro. Clinically, R321 symmetric dimethylation status was associated with malignant progression of human hepatocellular carcinoma, where it served as an independent risk factor of poor prognosis. By showing how PRMT5-induced methylation of SREBP1a triggers hyperactivation of lipid biosynthesis, a key event in tumorigenesis, our findings suggest a new generalized strategy to selectively attack tumor metabolism.

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Cholesterol metabolism and colorectal cancers

Cited by 48 publications

References 52 publications

Dietary polyunsaturated fatty acids intake modifies the positive association between serum total cholesterol and colorectal cancer risk: the Rotterdam Study

Dietary polyunsaturated fatty acids intake modifies the positive association between serum total cholesterol and colorectal cancer risk: the Rotterdam Study

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

Arginine Methylation of SREBP1a via PRMT5 Promotes De Novo Lipogenesis and Tumor Growth

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