Nilotinib targets NEIL3-mediated fatty acid oxidation to promote anoikis in hepatocellular carcinoma cells
Year: 2026
Type: article
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.
Source: Frontiers in Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223159466