SLC25A20 promotes tumor growth by reprogramming energy metabolism in lung adenocarcinoma.
8 affiliations
- 1Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210093, China.
- 2The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine, Nanjing, 210003, China.
- 3State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China.
- 4Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China.
- 5The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine, Nanjing, 210003, China. [email protected].
- 6Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210093, China. [email protected].
- 7Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, 210093, China. [email protected].
- 8Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China. [email protected].
Abstract
Accumulating evidence has shown that the dysfunction of mitochondria, the multifunctional organelles in various cellular processes, is a pivotal event in the development of various diseases, including human cancers. The molecular alterations in tumors that promote metabolic diversity and distinct targetable dependencies remain poorly defined. The mitochondrial transporter SLC25A20, also known as carnitine-acylcarnitine translocase (CACT), is crucial for fatty acid β-oxidation (FAO) by importing acylcarnitines into the mitochondrial matrix. Here, we demonstrate that SLC25A20 is significantly upregulated in lung adenocarcinoma (LUAD) tissues and cells, and its expression correlates with poor patient survival. Gain- and loss-of-function experiments reveal that SLC25A20 promotes tumor cell proliferation, survival, migration, and invasion by enhancing FAO-associated mitochondrial bioenergetics and suppressing apoptosis. Mechanistically, SLC25A20-mediated FAO maintains mitochondrial function and supports oxidative phosphorylation (OXPHOS), thereby sustaining tumor bioenergetics and redox homeostasis. Pharmacological inhibition or genetic silencing of SLC25A20 impairs tumor growth in vivo. These findings establish SLC25A20 as a key metabolic driver in LUAD and suggest it may be a therapeutic target.
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BibTeX
@article{liu2026slc25a20,
title = {{SLC25A20 promotes tumor growth by reprogramming energy metabolism in lung adenocarcinoma.}},
author = {Xing Liu and Xiaoyu Song and Cong Gan and Ye Wang and Mingxin Ni and Min Zhang and Shaodi Wen and Yahui Cao and Changhua Yi and Man Tian and Apeng Chen},
journal = {Cell death \& disease},
year = {2026},
month = jul,
doi = {10.1038/s41419-026-09119-9},
url = {https://europepmc.org/article/MED/42897166},
note = {CC BY},
}
RIS
TY - JOUR
TI - SLC25A20 promotes tumor growth by reprogramming energy metabolism in lung adenocarcinoma.
AU - Xing Liu
AU - Xiaoyu Song
AU - Cong Gan
AU - Ye Wang
AU - Mingxin Ni
AU - Min Zhang
AU - Shaodi Wen
AU - Yahui Cao
AU - Changhua Yi
AU - Man Tian
AU - Apeng Chen
PY - 2026
DA - 2026/07/01
JO - Cell death & disease
DO - 10.1038/s41419-026-09119-9
UR - https://europepmc.org/article/MED/42897166
AB - Accumulating evidence has shown that the dysfunction of mitochondria, the multifunctional organelles in various cellular processes, is a pivotal event in the development of various diseases, including human cancers. The molecular alterations in tumors that promote metabolic diversity and distinct targetable dependencies remain poorly defined. The mitochondrial transporter SLC25A20, also known as carnitine-acylcarnitine translocase (CACT), is crucial for fatty acid β-oxidation (FAO) by importing acylcarnitines into the mitochondrial matrix. Here, we demonstrate that SLC25A20 is significantly upregulated in lung adenocarcinoma (LUAD) tissues and cells, and its expression correlates with poor patient survival. Gain- and loss-of-function experiments reveal that SLC25A20 promotes tumor cell proliferation, survival, migration, and invasion by enhancing FAO-associated mitochondrial bioenergetics and suppressing apoptosis. Mechanistically, SLC25A20-mediated FAO maintains mitochondrial function and supports oxidative phosphorylation (OXPHOS), thereby sustaining tumor bioenergetics and redox homeostasis. Pharmacological inhibition or genetic silencing of SLC25A20 impairs tumor growth in vivo. These findings establish SLC25A20 as a key metabolic driver in LUAD and suggest it may be a therapeutic target.
SN - 2041-4889
ER -