A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers

Pranavi Koppula; Guang Lei; Yilei Zhang; Yuelong Yan; Chao Mao; Lavanya Kondiparthi; Jiejun Shi; Xiaoguang Liu; Amber Horbath; Molina Das; Wei Li; Masha V. Poyurovsky; Kellen Olszewski; Boyi Gan

doi:10.1038/s41467-022-29905-1

Nature Communications (Apr 2022)

A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers

Pranavi Koppula,
Guang Lei,
Yilei Zhang,
Yuelong Yan,
Chao Mao,
Lavanya Kondiparthi,
Jiejun Shi,
Xiaoguang Liu,
Amber Horbath,
Molina Das,
Wei Li,
Masha V. Poyurovsky,
Kellen Olszewski,
Boyi Gan

Affiliations

Pranavi Koppula: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Guang Lei: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Yilei Zhang: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Yuelong Yan: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Chao Mao: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Lavanya Kondiparthi: Kadmon Corporation, LLC
Jiejun Shi: Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California
Xiaoguang Liu: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Amber Horbath: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Molina Das: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center
Wei Li: Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California
Masha V. Poyurovsky: Kadmon Corporation, LLC
Kellen Olszewski: Kadmon Corporation, LLC
Boyi Gan: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center

DOI: https://doi.org/10.1038/s41467-022-29905-1
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 16

Abstract

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KEAP1 mutations are frequently observed in NSCLC and lead to drug resistance. Here, the authors show that KEAP1 mutations in lung cancer cells leads to FSP1 upregulation through NRF2, resulting in ferroptosis resistance and radioresistance.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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