Evidence map›Paper›PMID 42827098›Full record

ArticleOncogene2026

TFAM loss drives oxaliplatin resistance by linking mtDNA release to STING-TBK1-mediated lysophagy.

Xiao-Xuan Wang, Xin-Han Wang, Zi-Hong Fan, Xiao-Feng Ding, Jian-Rui Zhong, Bing-Ming Zhu, Jie Lyu, Su-Jie Wang, Qing-Yu He, Yang Wang and 1 more

Abstract read
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In one paragraph

Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Xiao-Xuan Wang *State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Xin-Han Wang *MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Zi-Hong Fan *MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Xiao-Feng Ding *MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Jian-Rui ZhongMOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Bing-Ming ZhuDepartment of Clinical Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Jie LyuMOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Su-Jie WangMOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Qing-Yu HeState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China. tqyhe@email.jnu.edu.cn.
Yang WangMOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China. wangyang0507@jnu.edu.cn.ORCID http://orcid.org/0000-0001-6440-0204
Jing ZhangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China. zj6410@jnu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82372691
6 · The paper itself

Abstract

Acquired resistance to oxaliplatin (Oxa) represents a major clinical challenge in the treatment of colorectal cancer (CRC). Lysosomes are intracellular degradative organelles that enable cancer cells to adapt to metabolic and environmental stress; however, their precise regulatory roles in drug resistance remain poorly understood. Here, we report that lysosomal damage and its selective autophagic clearance (lysophagy) occur frequently in both Oxa-treated CRC cells and Oxa-resistant (OxaR) CRC cells. Through quantitative proteomics, we identified the significant downregulation of mitochondrial transcription factor A (TFAM) as a key event in Oxa-treated and OxaR cells. Mechanistically, Oxa-induced TFAM loss leads to mitochondrial DNA (mtDNA) leakage into the cytosol, which activates the STING-TBK1 signaling axis. This pathway subsequently enhances lysophagic flux, providing cancer cells with a survival advantage under Oxa stress. Crucially, pharmacological inhibition of TBK1 abrogates this adaptive lysophagy, restoring Oxa sensitivity and suppressing tumor growth in both xenograft and patient-derived organoid models. Collectively, our study reveals a novel TFAM-mtDNA-STING-TBK1 signaling axis that promotes chemoresistance through the co-option of lysophagy, highlighting TBK1 as a viable therapeutic target to overcome Oxa resistance in CRC.

Identifiers

PMID42827098

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