ArticleAutophagy2025
Endothelial F3-mediated autolysosome and lipid metabolism promote resistance to anti-VEGFA therapy in metastatic colorectal cancer.
Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with metastatic colorectal cancer (mCRC) to the liver exhibit poor survival rates. Chemotherapy combined with anti-vascular therapy has emerged as the standard treatment, but resistance to anti-VEGFA therapy inevitably develops. The metabolic reprogramming of tumor vascular endothelial cells (TECs) plays a crucial, yet still poorly understood, role in the development of therapeutic resistance. We identified lipid-rich and fatty acid oxidation (FAO)-activated proliferating TECs in fatty colorectal cancer liver metastasis (CRLM) that mediate resistance to anti-VEGFA treatment. The TEC-specific F3 protein inhibited the macroautophagy/autophagy-lysosome pathway through the MAPK/JNK-MAPK/ERK-TP53/p53 signaling axis, thereby prevented CPT1A protein degradation and enhanced FAO. F3 was also involved in promoting lipid uptake and lipophagy. This process promoted cellular FAO under conditions of fatty acids and anti-VEGFA stimulation. Targeting FAO proved effective in overcoming resistance to anti-VEGFA treatment. Our findings elucidated the role of lipid metabolism in therapy-resistant TECs in fatty CRLM and provided a theoretical foundation for further research on anti-VEGFA therapy resistance. Moreover, we underscored the potential of combining FAO inhibitors to enhance the efficacy of anti-angiogenic therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.