ACTL6A protects gastric cancer cells against ferroptosis through induction of glutathione synthesis

Ziqing Yang, Shaomin Zou, Yijing Zhang, Jieping Zhang, Peng Zhang, Lishi Xiao, Yunling Xie, Manqi Meng, Junyan Feng, Liang Kang (), Mong-Hong Lee () and Lekun Fang ()
Additional contact information
Ziqing Yang: The Sixth Affiliated Hospital, Sun Yat-sen University
Shaomin Zou: The Sixth Affiliated Hospital, Sun Yat-sen University
Yijing Zhang: The Sixth Affiliated Hospital, Sun Yat-sen University
Jieping Zhang: The Sixth Affiliated Hospital, Sun Yat-sen University
Peng Zhang: The Sixth Affiliated Hospital, Sun Yat-sen University
Lishi Xiao: The Sixth Affiliated Hospital, Sun Yat-sen University
Yunling Xie: The Sixth Affiliated Hospital, Sun Yat-sen University
Manqi Meng: The Sixth Affiliated Hospital, Sun Yat-sen University
Junyan Feng: The Sixth Affiliated Hospital, Sun Yat-sen University
Liang Kang: The Sixth Affiliated Hospital, Sun Yat-sen University
Mong-Hong Lee: The Sixth Affiliated Hospital, Sun Yat-sen University
Lekun Fang: The Sixth Affiliated Hospital, Sun Yat-sen University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Gastric cancer (GC), one of the most common malignant tumors in the world, exhibits a rapid metastasis rate and causes high mortality. Diagnostic markers and potential therapeutic targets for GCs are urgently needed. Here we show that Actin-like protein 6 A (ACTL6A), encoding an SWI/SNF subunit, is highly expressed in GCs. ACTL6A is found to be critical for regulating the glutathione (GSH) metabolism pathway because it upregulates γ-glutamyl-cysteine ligase catalytic subunit (GCLC) expression, thereby reducing reactive oxygen species (ROS) levels and inhibiting ferroptosis, a regulated form of cell death driven by the accumulation of lipid-based ROS. Mechanistic studies show that ACTL6A upregulates GCLC as a cotranscription factor with Nuclear factor (erythroid-derived 2)-like 2 (NRF2) and that the hydrophobic region of ACTL6A plays an important role. Our data highlight the oncogenic role of ACTL6A in GCs and indicate that inhibition of ACTL6A or GCLC could be a potential treatment strategy for GCs.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39901-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39901-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39901-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().