The Emerging Role of Obesity, Diet and Lipid Metabolism in Prostate Cancer

Ferro, Matteo; Terracciano, Daniela; Buonerba, Carlo; Lucarelli, Giuseppe; Bottero, Danilo; Perdonà, Sisto; Autorino, Riccardo; Serino, Alessandro; Cantiello, Francesco; Damiano, Rocco; Andraș, Iulia; Placido, Sabino De; Lorenzo, Giuseppe Di; Battaglia, Michele; Jereczek‐Fossa, Barbara Alicja; Mirone, Vincenzo; Cobelli, Ottavio De

doi:10.2217/fon-2016-0217

Cited by 58 publications

(52 citation statements)

References 82 publications

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“…Indeed, there is currently strong evidence supporting the existence of a clear association between alterations in the metabolic and hormonal status ( e.g . changes in circulating insulin, IGF1 and/or GH levels, obesity, diabetes) and a higher risk of developing, and an increased aggressiveness of, certain types of cancer, including prostate cancer . In this sense, we did not find any difference in circulating Gh levels in obese mice, likely because of the intrinsic pulsatility of Gh secretion.…”

Section: Discussioncontrasting

confidence: 44%

Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1

L‐López

Sarmento‐Cabral

Herrero‐Aguayo

et al. 2017

J Cellular Molecular Medi

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Obesity is a major health problem that courses with severe comorbidities and a drastic impairment of homeostasis and function of several organs, including the prostate gland (PG). The endocrine–metabolic regulatory axis comprising growth hormone (GH), insulin and IGF1, which is drastically altered under extreme metabolic conditions such as obesity, also plays relevant roles in the development, modulation and homeostasis of the PG. However, its implication in the pathophysiological interplay between obesity and prostate function is still to be elucidated. To explore this association, we used a high fat–diet obese mouse model, as well as in vitro primary cultures of normal‐mouse PG cells and human prostate cancer cell lines. This approach revealed that most of the components of the GH/insulin/IGF1 regulatory axis are present in PGs, where their expression pattern is altered under obesity conditions and after an acute insulin treatment (e.g. Igfbp3), which might have some pathophysiological implications. Moreover, our results demonstrate, for the first time, that the PG becomes severely insulin resistant under diet‐induced obesity in mice. Finally, use of in vitro approaches served to confirm and expand the conception that insulin and IGF1 play a direct, relevant role in the control of normal and pathological PG cell function. Altogether, these results uncover a fine, germane crosstalk between the endocrine–metabolic status and the development and homeostasis of the PG, wherein key components of the GH, insulin and IGF1 axes could play a relevant pathophysiological role.

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Section: Discussioncontrasting

confidence: 44%

Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1

L‐López

Sarmento‐Cabral

Herrero‐Aguayo

et al. 2017

J Cellular Molecular Medi

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“…Obesity has also been strongly associated with ovarian and breast cancer and with other types of cancer . For prostate cancer, obesity appears to increase the risk of more aggressive disease, which may be because of lower androgen levels, while simultaneously increasing the risk of more indolent disease . That young Americans have become increasingly obese over the same years as their prostate cancer increase suggests another contributing factor, although the decreases in both since 2010 through 2012 and the increasing incidence in countries that have not had an obesity epidemic counter this explanation.…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer in young men: An emerging young adult and older adolescent challenge

Bleyer

Spreafico

Barr

2019

Cancer

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Background Recent observations suggest that prostate cancer is an increasing disease among older adolescents and young adults. Methods Incidence, mortality, and survival data were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results program and the Institute for Health Metrics and Evaluation Global Burden of Disease database. Results Worldwide, the incidence of prostate cancer has increased in all groups between ages 15 and 40 years and increased globally at a steady rate averaging 2% per year since 1990 (P < .01). In the United States, this age group was >6 times more likely than older men to have distant disease at diagnosis. Stage for stage, their survival rate improved less than in older men. Whereas the overall 5‐year relative survival rate in the United States for men diagnosed between ages 40 and 80 years was between 95% and 100%, it was 30% in those aged 15 to 24 years, 50% in those aged 20 to 29 years, and 80% in those aged 25 to 34 years. Conclusions Prostate cancer in older adolescent and young adult men has increased in most countries. There is some evidence that this may be caused in part by underdiagnosis, prostate‐specific antigen screening, and overdiagnosis. It also may be caused by trends in obesity, physical inactivity, HPV infection, substance exposure, environmental carcinogens, and/or referral patterns. How the biology of these cancers differs from that in older men and how the etiologies vary from country to country remain to be determined.

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“…Recent evidence indicates that significant different lipid metabolites and expression of lipid metabolic enzymes are detected in cancer. These lipid metabolites are associated with cell proliferation, cellular membrane synthesis and signaling molecules (4)(5)(6). Some of the dysregulated metabolic enzymes, such as the glucose transporter 1 (GLUT1), hexokinase 2, lactate dehydrogenase A, glutaminase and fatty acid synthase have been demonstrated to be novel therapeutic targets of cancers (7).…”

Section: Introductionmentioning

confidence: 99%

Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

et al. 2017

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Abstract. The lipid metabolic enzymes are considered candidate therapeutic targets for breast cancer. Long-chain acyl-coenzyme A (CoA) synthase (ACSL) is one of lipid metabolic enzymes and converts free-fatty acid to fatty acid-CoA. Five ACSL isoforms including ACSL1, ACSL3, ACSL4, ACSL5 and ACSL6 are identified in human. High ACSL4 expression has been observed in aggressive breast cancer phenotype. However, the role of other isoforms is still little-known. We therefore, analyzed the expression of ACSL isoforms in each subtype of breast cancer within METABRIC dataset and cancer cell line encyclopedia dataset. The expression levels of ACSL1, ACSL4 and ACSL5 in estrogen receptor (ER)-negative group were higher than that in ER-positive group. Similar expression pattern was detected among breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Treatment of ACSL inhibitor triacsin C which inhibited enzyme activity of ACSL 1, 3, 4 and 5 suppressed cell growth of MCF-7 and MDA-MB-231. Our results further showed that high ACSL5 expression was associated with good prognosis in patients with both ER-positive and ER-negative breast cancer through KM plotter analysis. These results suggest that ACSL1, ACSL4 and ACSL5 expression is regulated by ER signaling pathways and ACSL5 is a potential novel biomarker for predicting prognosis of breast cancer patients.

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The Emerging Role of Obesity, Diet and Lipid Metabolism in Prostate Cancer

Cited by 58 publications

References 82 publications

Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1

Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1

Prostate cancer in young men: An emerging young adult and older adolescent challenge

Association of long-chain acyl-coenzyme A synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance

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