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Peer-reviewedCC BY 4.0Frontiers in Oncology

Nilotinib targets NEIL3-mediated fatty acid oxidation to promote anoikis in hepatocellular carcinoma cells

  • Biao Tang1
  • Zhicheng Shen1
  • Jining Zeng1
  • Kaida Wei1
  • Xin Tang1
  • Min Huang1
  • Huari He1
  • Wangning Xia1
  • Xintao Liu1
  1. 1Department of Hepatobiliary Pancreatic Spleen Surgery, The Central Hospital of Yongzhou
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Abstract

Background: Overcoming anoikis is a critical step for the survival of metastatic cancer cells. Despite extensive research, resistance to anoikis in hepatocellular carcinoma (HCC) cells remains a major and yet unresolved challenge.

Methods: NEIL3 expression in HCC was assessed via bioinformatics and RT-qPCR. Cell viability was measured using CCK-8. Anoikis was evaluated through live/dead staining, flow cytometry, and Western blot. Fatty acid oxidation (FAO) was evaluated by oxygen consumption rates and ATP levels. The NEIL3-Nilotinib binding was predicted by molecular docking and validated through CETSA and DARTS. Nilotinib’s inhibition of tumor growth by targeting NEIL3 was confirmed in a xenograft mouse model.

Results: NEIL3 was highly expressed in HCC patient tissues and cells. NEIL3 knockdown inhibited HCC cell survival by inducing anoikis. Mechanistic studies revealed that NEIL3 was enriched in FAO pathways, and its upregulation activated FAO to suppress anoikis in HCC cells. Nilotinib specifically bound to NEIL3, which significantly counteracted inhibition of anoikis by NEIL3 overexpression and delayed tumor growth.

Conclusion: By activating FAO, NEIL3 suppresses anoikis in HCC cells, a process reversible by Nilotinib through targeting NEIL3, revealing NEIL3 as a therapeutic target and Nilotinib as a candidate drug for HCC.

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Cite

BibTeXRIS
BibTeX
@article{tang2026nilotinib,
  title = {{Nilotinib targets NEIL3-mediated fatty acid oxidation to promote anoikis in hepatocellular carcinoma cells}},
  author = {Biao Tang and Zhicheng Shen and Jining Zeng and Kaida Wei and Xin Tang and Min Huang and Huari He and Wangning Xia and Xintao Liu},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1810429},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1810429/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Nilotinib targets NEIL3-mediated fatty acid oxidation to promote anoikis in hepatocellular carcinoma cells
AU  - Biao Tang
AU  - Zhicheng Shen
AU  - Jining Zeng
AU  - Kaida Wei
AU  - Xin Tang
AU  - Min Huang
AU  - Huari He
AU  - Wangning Xia
AU  - Xintao Liu
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1810429
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1810429/full
AB  - Background: Overcoming anoikis is a critical step for the survival of metastatic cancer cells. Despite extensive research, resistance to anoikis in hepatocellular carcinoma (HCC) cells remains a major and yet unresolved challenge.  Methods: NEIL3 expression in HCC was assessed via bioinformatics and RT-qPCR. Cell viability was measured using CCK-8. Anoikis was evaluated through live/dead staining, flow cytometry, and Western blot. Fatty acid oxidation (FAO) was evaluated by oxygen consumption rates and ATP levels. The NEIL3-Nilotinib binding was predicted by molecular docking and validated through CETSA and DARTS. Nilotinib’s inhibition of tumor growth by targeting NEIL3 was confirmed in a xenograft mouse model.  Results: NEIL3 was highly expressed in HCC patient tissues and cells. NEIL3 knockdown inhibited HCC cell survival by inducing anoikis. Mechanistic studies revealed that NEIL3 was enriched in FAO pathways, and its upregulation activated FAO to suppress anoikis in HCC cells. Nilotinib specifically bound to NEIL3, which significantly counteracted inhibition of anoikis by NEIL3 overexpression and delayed tumor growth.  Conclusion: By activating FAO, NEIL3 suppresses anoikis in HCC cells, a process reversible by Nilotinib through targeting NEIL3, revealing NEIL3 as a therapeutic target and Nilotinib as a candidate drug for HCC.
SN  - 2234-943X
ER  -