Epithelial-mesenchymal transition and H2O2 signaling – a driver of disease progression and a vulnerability in cancers

Anna V. Milton; David B. Konrad

doi:10.1515/hsz-2021-0341

Artikel

Epithelial-mesenchymal transition and H₂O₂ signaling – a driver of disease progression and a vulnerability in cancers

Anna V. Milton

Anna V. Milton grew up in the Swedish countryside close to Vimmerby in Småland. To follow her academic interests, she moved to Uppsala where she obtained a B.Sc. in biomedicine followed by a M.Sc. in molecular medicine. Anna performed her Master’s thesis at the Biomedical Center at the Ludwig Maximilian University of Munich where she studied the epigenetic control of endogenous retroviruses. Equipped with a rigid and broad background in biomedical research, Anna’s specific interests lie in uncovering disease mechanisms. This led her to pursue a PhD in the Konrad laboratory, where she uses (chemo)proteomics methods to uncover vulnerabilities in therapy-resistant cancer cells for the development of novel drugs to treat advanced Non-Small Cell Lung Cancer.
und David B. Konrad

David B. Konrad studied chemistry and biochemistry at the Ludwig Maximilian University (LMU) Munich and received his M.Sc. in 2013. During his Master’s studies, he worked as a visiting researcher in the group of Dean Toste at the University of California, Berkeley and the group of Benjamin List at the Max Planck Institute for Coal Research in Mülheim a. d. Ruhr. In 2014, David joined the group of Dirk Trauner for his graduate studies to work towards an asymmetric synthesis of tetrodotoxin and methods to red-shift photopharmaceuticals. After graduating in 2018 summa cum laude, David moved to the Scripps Research Institute in La Jolla as a postdoctoral fellow under the guidance of Benjamin Cravatt. As part of the return phase of his fellowship, David joined the group of Ivan Huc at the Department of Pharmacy of the LMU Munich, where he transitioned to an independent group leader in 2021.

Veröffentlicht/Copyright: 17. Januar 2022

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Aus der Zeitschrift Biological Chemistry Band 403 Heft 4

Abstract

Mutation-selective drugs constitute a great advancement in personalized anticancer treatment with increased quality of life and overall survival in cancers. However, the high adaptability and evasiveness of cancers can lead to disease progression and the development of drug resistance, which cause recurrence and metastasis. A common characteristic in advanced neoplastic cancers is the epithelial-mesenchymal transition (EMT) which is strongly interconnected with H₂O₂ signaling, increased motility and invasiveness. H₂O₂ relays its signal through the installation of oxidative posttranslational modifications on cysteines. The increased H₂O₂ levels that are associated with an EMT confer a heightened sensitivity towards the induction of ferroptosis as a recently discovered vulnerability.

Keywords: cysteine modifications; ferroptosis; hydrogen peroxide signaling; oxidative posttranslational modifications; reactive oxygen species; targeted therapy

Corresponding author: David B. Konrad, Department of Pharmacy, Ludwig Maximilian University of Munich, Butenandtstr. 5-13, Haus C, D-81377 Munich, Germany, E-mail: david.konrad@cup.lmu.de

Funding source: Fonds der Chemischen Industrie 10.13039/100007215

Funding source: LMUexcellent Junior Researcher Fund 10.13039/501100005722

Funding source: DFG SPP2306 10.13039/501100001659

Award Identifier / Grant number: KO 5903/2-1

Funding source: Excellence Strategy of the Federal Government and the Länder

About the authors

Anna V. Milton

Anna V. Milton grew up in the Swedish countryside close to Vimmerby in Småland. To follow her academic interests, she moved to Uppsala where she obtained a B.Sc. in biomedicine followed by a M.Sc. in molecular medicine. Anna performed her Master’s thesis at the Biomedical Center at the Ludwig Maximilian University of Munich where she studied the epigenetic control of endogenous retroviruses. Equipped with a rigid and broad background in biomedical research, Anna’s specific interests lie in uncovering disease mechanisms. This led her to pursue a PhD in the Konrad laboratory, where she uses (chemo)proteomics methods to uncover vulnerabilities in therapy-resistant cancer cells for the development of novel drugs to treat advanced Non-Small Cell Lung Cancer.

David B. Konrad

David B. Konrad studied chemistry and biochemistry at the Ludwig Maximilian University (LMU) Munich and received his M.Sc. in 2013. During his Master’s studies, he worked as a visiting researcher in the group of Dean Toste at the University of California, Berkeley and the group of Benjamin List at the Max Planck Institute for Coal Research in Mülheim a. d. Ruhr. In 2014, David joined the group of Dirk Trauner for his graduate studies to work towards an asymmetric synthesis of tetrodotoxin and methods to red-shift photopharmaceuticals. After graduating in 2018 summa cum laude, David moved to the Scripps Research Institute in La Jolla as a postdoctoral fellow under the guidance of Benjamin Cravatt. As part of the return phase of his fellowship, David joined the group of Ivan Huc at the Department of Pharmacy of the LMU Munich, where he transitioned to an independent group leader in 2021.

Acknowledgements

The authors are grateful to Prof. Dr. Ivan Huc for his strong support and mentorship. Figures in this manuscript were, in part, created with BioRender.com.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: DBK acknowledges funding from the Fonds der Chemischen Industrie through a Liebig Fellowship, the DFG SPP2306 (KO 5903/2-1) and the LMUexcellent Junior Researcher Fund which is supported by the Federal Ministry of Education and Research (BMBF) and the Free State of Bavaria under the Excellence Strategy of the Federal Government and the Länder. AVM thanks the Department of Pharmacy for her Ph.D. position.
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2021-08-06

Accepted: 2021-12-18

Published Online: 2022-01-17

Published in Print: 2022-03-28

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https://doi.org/10.1515/hsz-2021-0341

Schlagwörter für diesen Artikel

cysteine modifications; ferroptosis; hydrogen peroxide signaling; oxidative posttranslational modifications; reactive oxygen species; targeted therapy