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Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| In: | Cancer Research, 79, 2019, 10, S. 2494-2510 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Madak-Erdogan, Zeynep Band, Shoham Zhao, Yiru C. Smith, Brandi P. Kulkoyluoglu-Cotul, Eylem Zuo, Qianying Santaliz Casiano, Ashlie Wrobel, Kinga Rossi, Gianluigi Smith, Rebecca L. Kim, Sung Hoon Katzenellenbogen, John A. Johnson, Mariah L. Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Flaws, Jodi A. Madak-Erdogan, Zeynep Band, Shoham Zhao, Yiru C. Smith, Brandi P. Kulkoyluoglu-Cotul, Eylem Zuo, Qianying Santaliz Casiano, Ashlie Wrobel, Kinga Rossi, Gianluigi Smith, Rebecca L. Kim, Sung Hoon Katzenellenbogen, John A. Johnson, Mariah L. Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Flaws, Jodi A. |
|---|---|
| author |
Madak-Erdogan, Zeynep Band, Shoham Zhao, Yiru C. Smith, Brandi P. Kulkoyluoglu-Cotul, Eylem Zuo, Qianying Santaliz Casiano, Ashlie Wrobel, Kinga Rossi, Gianluigi Smith, Rebecca L. Kim, Sung Hoon Katzenellenbogen, John A. Johnson, Mariah L. Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Flaws, Jodi A. |
| spellingShingle |
Madak-Erdogan, Zeynep Band, Shoham Zhao, Yiru C. Smith, Brandi P. Kulkoyluoglu-Cotul, Eylem Zuo, Qianying Santaliz Casiano, Ashlie Wrobel, Kinga Rossi, Gianluigi Smith, Rebecca L. Kim, Sung Hoon Katzenellenbogen, John A. Johnson, Mariah L. Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Flaws, Jodi A. Cancer Research Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling Cancer Research Oncology |
| author_sort |
madak-erdogan, zeynep |
| spelling |
Madak-Erdogan, Zeynep Band, Shoham Zhao, Yiru C. Smith, Brandi P. Kulkoyluoglu-Cotul, Eylem Zuo, Qianying Santaliz Casiano, Ashlie Wrobel, Kinga Rossi, Gianluigi Smith, Rebecca L. Kim, Sung Hoon Katzenellenbogen, John A. Johnson, Mariah L. Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Flaws, Jodi A. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-18-2849 <jats:title>Abstract</jats:title><jats:sec><jats:title /><jats:p>Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women.</jats:p></jats:sec><jats:sec><jats:title>Significance:</jats:title><jats:p>These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.</jats:p></jats:sec> Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling Cancer Research |
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10.1158/0008-5472.can-18-2849 |
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American Association for Cancer Research (AACR), 2019 |
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American Association for Cancer Research (AACR), 2019 |
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0008-5472 1538-7445 |
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| title |
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_unstemmed |
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_full |
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_fullStr |
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_full_unstemmed |
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_short |
Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_sort |
free fatty acids rewire cancer metabolism in obesity-associated breast cancer via estrogen receptor and mtor signaling |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-18-2849 |
| publishDate |
2019 |
| physical |
2494-2510 |
| description |
<jats:title>Abstract</jats:title><jats:sec><jats:title /><jats:p>Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women.</jats:p></jats:sec><jats:sec><jats:title>Significance:</jats:title><jats:p>These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.</jats:p></jats:sec> |
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| author | Madak-Erdogan, Zeynep, Band, Shoham, Zhao, Yiru C., Smith, Brandi P., Kulkoyluoglu-Cotul, Eylem, Zuo, Qianying, Santaliz Casiano, Ashlie, Wrobel, Kinga, Rossi, Gianluigi, Smith, Rebecca L., Kim, Sung Hoon, Katzenellenbogen, John A., Johnson, Mariah L., Patel, Meera, Marino, Natascia, Storniolo, Anna Maria V., Flaws, Jodi A. |
| author_facet | Madak-Erdogan, Zeynep, Band, Shoham, Zhao, Yiru C., Smith, Brandi P., Kulkoyluoglu-Cotul, Eylem, Zuo, Qianying, Santaliz Casiano, Ashlie, Wrobel, Kinga, Rossi, Gianluigi, Smith, Rebecca L., Kim, Sung Hoon, Katzenellenbogen, John A., Johnson, Mariah L., Patel, Meera, Marino, Natascia, Storniolo, Anna Maria V., Flaws, Jodi A., Madak-Erdogan, Zeynep, Band, Shoham, Zhao, Yiru C., Smith, Brandi P., Kulkoyluoglu-Cotul, Eylem, Zuo, Qianying, Santaliz Casiano, Ashlie, Wrobel, Kinga, Rossi, Gianluigi, Smith, Rebecca L., Kim, Sung Hoon, Katzenellenbogen, John A., Johnson, Mariah L., Patel, Meera, Marino, Natascia, Storniolo, Anna Maria V., Flaws, Jodi A. |
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| description | <jats:title>Abstract</jats:title><jats:sec><jats:title /><jats:p>Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women.</jats:p></jats:sec><jats:sec><jats:title>Significance:</jats:title><jats:p>These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.</jats:p></jats:sec> |
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| spelling | Madak-Erdogan, Zeynep Band, Shoham Zhao, Yiru C. Smith, Brandi P. Kulkoyluoglu-Cotul, Eylem Zuo, Qianying Santaliz Casiano, Ashlie Wrobel, Kinga Rossi, Gianluigi Smith, Rebecca L. Kim, Sung Hoon Katzenellenbogen, John A. Johnson, Mariah L. Patel, Meera Marino, Natascia Storniolo, Anna Maria V. Flaws, Jodi A. 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-18-2849 <jats:title>Abstract</jats:title><jats:sec><jats:title /><jats:p>Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women.</jats:p></jats:sec><jats:sec><jats:title>Significance:</jats:title><jats:p>These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.</jats:p></jats:sec> Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling Cancer Research |
| spellingShingle | Madak-Erdogan, Zeynep, Band, Shoham, Zhao, Yiru C., Smith, Brandi P., Kulkoyluoglu-Cotul, Eylem, Zuo, Qianying, Santaliz Casiano, Ashlie, Wrobel, Kinga, Rossi, Gianluigi, Smith, Rebecca L., Kim, Sung Hoon, Katzenellenbogen, John A., Johnson, Mariah L., Patel, Meera, Marino, Natascia, Storniolo, Anna Maria V., Flaws, Jodi A., Cancer Research, Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling, Cancer Research, Oncology |
| title | Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_full | Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_fullStr | Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_full_unstemmed | Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_short | Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| title_sort | free fatty acids rewire cancer metabolism in obesity-associated breast cancer via estrogen receptor and mtor signaling |
| title_unstemmed | Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-18-2849 |