Cysteine depletion induces pancreatic tumor ferroptosis in mice-Reference-Cited by-同舟云学术

Cysteine depletion induces pancreatic tumor ferroptosis in mice

Published:2020-04-03 Issue:6486 Volume:368 Page:85-89
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Badgley Michael A.¹²^ORCID,Kremer Daniel M.³⁴^ORCID,Maurer H. Carlo¹²⁵^ORCID,DelGiorno Kathleen E.⁶^ORCID,Lee Ho-Joon³⁴^ORCID,Purohit Vinee³⁴^ORCID,Sagalovskiy Irina R.¹²^ORCID,Ma Alice¹²^ORCID,Kapilian Jonathan¹²^ORCID,Firl Christina E. M.¹²,Decker Amanda R.¹²^ORCID,Sastra Steve A.¹²,Palermo Carmine F.¹²,Andrade Leonardo R.⁷^ORCID,Sajjakulnukit Peter³⁴^ORCID,Zhang Li⁴⁸^ORCID,Tolstyka Zachary P.³⁴,Hirschhorn Tal⁹^ORCID,Lamb Candice¹⁰^ORCID,Liu Tong²¹¹¹²,Gu Wei²¹¹¹²^ORCID,Seeley E. Scott¹³¹⁴,Stone Everett¹⁰¹⁵,Georgiou George¹⁵^ORCID,Manor Uri⁷^ORCID,Iuga Alina²¹²^ORCID,Wahl Geoffrey M.⁶^ORCID,Stockwell Brent R.⁹^ORCID,Lyssiotis Costas A.³⁴¹⁶^ORCID,Olive Kenneth P.¹²^ORCID

Affiliation:

1. Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.

2. Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.

3. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.

4. Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.

5. Klinikum rechts der Isar, II, Medizinische Klinik, Technische Universität München, 81675, Munich, Germany.

6. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

7. Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

8. Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48105, USA.

9. Departments of Biological Sciences and Chemistry, Columbia University, New York, NY 10027, USA.

10. Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.

11. Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.

12. Department of Pathology, Columbia University Medical Center, New York, NY 10032, USA.

13. Department of Pathology, University of California, San Francisco, CA 94143, USA.

14. Salvo Therapeutics, San Francisco, CA 94117, USA.

15. Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.

16. Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

Ferroptotic cell death and cancer Cell death can occur through different mechanisms, several of which are being explored as potential targets for cancer treatment. One form of cell death that has attracted recent interest is ferroptosis, which is triggered by high intracellular levels of lipid reactive oxygen species. Pancreatic cancer cells have high levels of reactive oxygen species but manage to avoid ferroptosis by importing extracellular cysteine. Studying mice bearing pancreatic tumors, Badgley et al. found that administration of a drug inhibiting cysteine import induced tumor-selective ferroptosis and inhibited tumor growth. Further work will be required to determine whether this therapeutic strategy will be effective in human pancreatic cancer, a tumor type for which new treatments are urgently needed. Science , this issue p. 85

Funder

National Institutes of Health

National Cancer Institute

Damon Runyon Cancer Research Foundation

U.S. Department of Education

U.S. Department of Defense

Lustgarten Foundation

Sidney Kimmel Foundation for Cancer Research

Pancreatic Cancer Action Network

The V Foundation for Cancer Research

Waitt Foundation

Salk Women and Special Science Award