FoxM1-dependent and fatty acid oxidation-mediated ROS modulation is a cell-intrinsic drug resistance mechanism in cancer stem-like cells.

Redox Biology
Hae-Ji ChoiJae-Ho Cheong

Abstract

Increased oxidative phosphorylation (OXPHOS) and reactive oxygen species (ROS) levels are inherently linked. ROS are essential signaling molecules, with detrimental effects when produced in excess during chemotherapy, leading to cell death. Cancer stem-like cells (CSCs) are a subpopulation of tumor cells resistant to chemotherapy, highly invasive and metastagenic, driving malignant cancer behavior. In this study, we demonstrated that CSCs exhibit increased OXPHOS but paradoxically low ROS levels. Considering the detrimental effects of large amounts of ROS, CSCs have developed potential mechanisms for quenching excess ROS to maintain redox homeostasis. We aimed to investigate the distinct metabolic features and mechanisms of ROS regulation in gastric CSCs and explore potential therapeutic strategies targeting CSCs. Human gastric cancer cell lines, AGS and MKN1, were subjected to liquid chromatography/mass spectrometry-based metabolomic and microarray analyses. Mitochondrial properties such as mitochondrial mass, membrane potential, and ROS were assessed by flow cytometric analysis. CSCs with increased OXPHOS levels maintained low ROS levels by coupling FoxM1-dependent Prx3 expression and fatty acid oxidation-mediated NADPH regen...Continue Reading

References

Aug 22, 2009·The EMBO Journal·Hyun Jung ParkPradip Raychaudhuri
Jun 10, 2010·Cancer Research·Janai R CarrPradip Raychaudhuri
Sep 26, 2013·Nature Reviews. Cancer·Benjamin Beck, Cédric Blanpain
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May 9, 2014·Nature·Jing FanJoshua D Rabinowitz
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Nov 2, 2018·Journal of Experimental & Clinical Cancer Research : CR·Haotian YangXiaowen Liang
Feb 17, 2019·Archives of Pharmacal Research·Min-Kyue Shin, Jae-Ho Cheong

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Citations

Oct 2, 2020·Cancers·Atsushi Tanabe, Hiroeki Sahara
Feb 10, 2021·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Jingyuan WangDongdong Sun
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sepideh MirzaeiKwang-Seok Ahn
Jan 14, 2022·Molecular Cancer·Yuanyuan An, Hua Duan

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Methods Mentioned

BETA
PCR
protein concentration assay
flow cytometry
fluorescence-activated cell sorting

Software Mentioned

ssGSEA
GraphPad Prism

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