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FADS2-mediated fatty acid desaturation and cholesterol esterification are signatures of metabolic reprogramming during melanoma progression

View ORCID ProfileHyeon Jeong Lee, Zhicong Chen, Marianne Collard, Jiaji G Chen, Muzhou Wu, Rhoda M Alani, Ji-Xin Cheng
doi: https://doi.org/10.1101/2020.07.12.198903
Hyeon Jeong Lee
1Photonics Center, Boston University, Boston, MA 02215, USA
2College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, China
3Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China
4Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA
8These authors contributed equally: Hyeon Jeong Lee, Zhicong Chen
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Zhicong Chen
1Photonics Center, Boston University, Boston, MA 02215, USA
4Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA
5Department of Urology, Peking University First Hospital, Beijing 100034, China
8These authors contributed equally: Hyeon Jeong Lee, Zhicong Chen
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Marianne Collard
6Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
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Jiaji G Chen
6Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
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Muzhou Wu
6Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
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Rhoda M Alani
6Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
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  • For correspondence: jxcheng@bu.edu alani@bu.edu
Ji-Xin Cheng
1Photonics Center, Boston University, Boston, MA 02215, USA
4Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA
7Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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  • For correspondence: jxcheng@bu.edu alani@bu.edu
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Abstract

Identifying metabolic alterations in disease progression has been challenged by difficulties in tracking metabolites at sub-cellular level. Here, by high-resolution stimulated Raman scattering and pump-probe imaging and spectral phasor analysis of melanoma cells grouped by MITF/AXL expression pattern and of human patient tissues paired by primary and metastatic status, we identify a metabolic switch from a pigment-containing phenotype in low-grade melanoma to a lipid-rich phenotype in metastatic melanoma. The lipids found in MITFlow/AXLhigh melanoma cells contain high levels of cholesteryl ester (CE) and unsaturated fatty acid species. Elevated fatty acid uptake activity in MITFlow/AXLhigh melanoma contributes to the lipid-rich phenotype, and inhibiting fatty acid uptake suppresses cell migration. Importantly, monounsaturated sapienate is identified as an essential fatty acid that effectively promotes cancer migration. Blocking either FADS2-mediated lipid desaturation or SOAT-mediated cholesterol esterification effectively suppresses the migration capacity of melanoma in vitro and in vivo, indicating the therapeutic potential of targeting these metabolic pathways in metastatic melanoma. Collectively, our results reveal metabolic reprogramming during melanoma progression, and highlight metabolic signatures that could serve as targets for metastatic melanoma treatment and diagnosis.

Competing Interest Statement

The authors have declared no competing interest.

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Posted July 12, 2020.
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FADS2-mediated fatty acid desaturation and cholesterol esterification are signatures of metabolic reprogramming during melanoma progression
Hyeon Jeong Lee, Zhicong Chen, Marianne Collard, Jiaji G Chen, Muzhou Wu, Rhoda M Alani, Ji-Xin Cheng
bioRxiv 2020.07.12.198903; doi: https://doi.org/10.1101/2020.07.12.198903
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FADS2-mediated fatty acid desaturation and cholesterol esterification are signatures of metabolic reprogramming during melanoma progression
Hyeon Jeong Lee, Zhicong Chen, Marianne Collard, Jiaji G Chen, Muzhou Wu, Rhoda M Alani, Ji-Xin Cheng
bioRxiv 2020.07.12.198903; doi: https://doi.org/10.1101/2020.07.12.198903

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