Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

Imir, Ozan Berk; Kaminsky, Alanna Zoe; Zuo, Qianying; Liu, Yu-Jeh; Singh, Ratnakar; Spinella, Michael J.; Irudayaraj, Joseph; Hu, Wen‐Yang; Prins, Gail S.; Madak-Erdoğan, Zeynep

doi:10.3390/nu13113902

Cited by 21 publications

(21 citation statements)

References 55 publications

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“…Additionally, recent studies have reported PFAS-mediated alterations of epigenetic regulators, such as DNA methyltransferases, ten-eleven translocation methylcytosine dioxygenases, and histone deacetylase enzymes in different mouse organs and human cell lines [ 106 , 107 , 110 , 117 , 118 , 119 ]. PFAS-mediated effects on histone modifications and microRNAs have also been described [ 49 , 106 , 107 , 118 , 120 , 121 , 122 ].…”

Section: Potential Mechanisms Of Pfas Carcinogenesismentioning

confidence: 99%

“…Of note, these actions are mediated, in part, through PPARα, providing the potential for enhanced tumor promotion. We recently showed that PFOS exposure and a high-fat diet synergize to increase prostate cancer xenograft growth in mice [ 122 , 162 ]. PFOS treatment increased glucose metabolism and pyruvate production in prostate cancer cells [ 122 ].…”

Section: The Case For Prostate Cancermentioning

confidence: 99%

“…We recently showed that PFOS exposure and a high-fat diet synergize to increase prostate cancer xenograft growth in mice [ 122 , 162 ]. PFOS treatment increased glucose metabolism and pyruvate production in prostate cancer cells [ 122 ]. In addition, we demonstrated that an enhancement of glycine and serine metabolism and enhanced glucose metabolism, through the Warburg effect in human prostate stem-progenitor cells, took place in response to PFOA and PFOS exposures [ 162 ].…”

Section: The Case For Prostate Cancermentioning

confidence: 99%

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Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer

Boyd

Ahmad

Singh

et al. 2022

Cancers

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Poly- and perfluoroalkylated substances (PFAS) are chemicals that persist and bioaccumulate in the environment and are found in nearly all human populations through several routes of exposure. Human occupational and community exposure to PFAS has been associated with several cancers, including cancers of the kidney, testis, prostate, and liver. While evidence suggests that PFAS are not directly mutagenic, many diverse mechanisms of carcinogenicity have been proposed. In this mini-review, we organize these mechanisms into three major proposed pathways of PFAS action—metabolism, endocrine disruption, and epigenetic perturbation—and discuss how these distinct but interdependent pathways may explain many of the proposed pro-carcinogenic effects of the PFAS class of environmental contaminants. Notably, each of the pathways is predicted to be highly sensitive to the dose and window of exposure which may, in part, explain the variable epidemiologic and experimental evidence linking PFAS and cancer. We highlight testicular and prostate cancer as models to validate this concept.

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Section: Potential Mechanisms Of Pfas Carcinogenesismentioning

confidence: 99%

Section: The Case For Prostate Cancermentioning

confidence: 99%

Section: The Case For Prostate Cancermentioning

confidence: 99%

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Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer

Boyd

Ahmad

Singh

et al. 2022

Cancers

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“…Histone 3 displays altered acetylation at lysine 4, 9, and 27 in breast cancer cells that fail to respond to ER antagonists (65)(66)(67). Systemic metabolic changes impact hormone-dependent cancer cell metabolism (41,68) and composition of histone marks (39,69), and response to therapies (19,41). Our findings suggest an altered ERα activity in MBC cells residing in the liver microenvironment, and a role for metabolic and epigenetic enzymes to interact with ER in a Fulv-dependent manner to locally change epigenetic marks, which would lead to altered response to ERα antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…To visualize the separation between No ECM and Liver ECM groups' metabolic profiles VIP scores for the top 25 metabolites that discriminated between treatment groups were calculated and displayed using the Partial least squares discriminant analysis (PLS-DA) tool. Enrichment analysis and pathway analysis were used to identify metabolic pathways associated with enriched metabolites (fold change >2 or <0.05) as previously described (39)(40)(41)(42).…”

Section: Metabolomics Analysismentioning

confidence: 99%

Targeting Metabolic Adaptations in the Breast Cancer–Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy

Zuo

Mogol

Liu

et al. 2022

Molecular Cancer Research

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Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant (Fulv) as standard-of-care. Yet, among such patients, metastasis in the liver is associated with reduced overall survival compared to other metastasis sites. The factors underlying the reduced responsiveness of liver metastases to ER-targeting agents remain unknown, impeding the development of more effective treatment approaches to improve outcomes for patients with ER+ liver metastases. We therefore evaluated site-specific changes in MBC cells and determined the mechanisms through which the liver metastatic niche specifically influences ER+ tumor metabolism and drug resistance. We characterized ER activity of MBC cells both in vitro, using a novel system of tissue-specific extracellular matrix hydrogels representing the stroma of ER+ tumor metastatic sites (liver, lung and bone), and in vivo, in liver and lung metastasis mouse models. ER+ metastatic liver tumors and MBC cells grown in liver hydrogels displayed upregulated expression of glucose metabolism enzymes in response to Fulv. Furthermore, differential ERα activity, but not expression, was detected in liver hydrogels. In vivo, increased glucose metabolism led to increased glycogen deposition in liver metastatic tumors, while a fasting-mimicking diet increased efficacy of Fulv treatment to reduce the metastatic burden. Our findings identify a novel mechanism of endocrine resistance driven by the liver tumor microenvironment. Implications: These results may guide the development of dietary strategies to circumvent drug resistance in liver metastasis, with potential applicability in other metastatic diseases.

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Per- and polyfluoroalkyl substances target and alter human prostate stem-progenitor cells

et al. 2022

Biochemical Pharmacology

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Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

Cited by 21 publications

References 55 publications

Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer

Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer

Targeting Metabolic Adaptations in the Breast Cancer–Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy

Per- and polyfluoroalkyl substances target and alter human prostate stem-progenitor cells

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