NHSL3 knockout alters sorafenib response, growth, and motility in two hepatocellular carcinoma cell models

Loss of Nance-Horan syndrome-like protein 3 (NHSL3) was associated with reduced clonogenic growth and migration in two hepatocellular carcinoma (HCC) cell models, while the observed response to sorafenib differed between the models. The study, summarized in an abstract in Molecular Biology Reports, examined NHSL3 function in Huh-7 and Hep3B cells rather than patients or animal models.

Researchers generated NHSL3 knockout clones in both cell lines using paired Cas9 nickase editing and obtained data from three independent biological experiments. In Huh-7 cells, NHSL3 loss increased sensitivity to sorafenib: the reported 24-hour half-maximal inhibitory concentration decreased from 13.4 µM to 5.8 µM. The knockout was associated with enrichment in G1 phase, a reduced S-phase fraction, and impaired clonogenic growth. Wound-closure and transwell assays also showed delayed wound closure and reduced migration. Invasion results varied according to sorafenib exposure and the duration of the assay.

The genotype-dependent sorafenib response was more modest in Hep3B cells and appeared at 48 hours. NHSL3 loss in that model was nevertheless associated with reduced clonogenic growth, as well as lower migration and invasion under vehicle-treated conditions. These findings indicate that the growth and motility phenotypes were more consistent across the two cell backgrounds than the drug-response phenotype. The study therefore does not support treating the effect of NHSL3 loss on sorafenib sensitivity as identical in every HCC cell model.

Molecular analyses in Huh-7 cells identified changes associated with epithelial-mesenchymal transition-related protein remodeling, including a blunted E-cadherin response to sorafenib and increased vimentin and N-cadherin levels. NHSL3 loss was also associated with lower basal phosphorylated RAF1 levels and with YAP/TAZ responses that depended on confluence and sorafenib exposure. The available report is limited to cell models and the abstract; it does not establish the relevance of these observations to clinical treatment responses or patient outcomes.

Subject of Research: NHSL3 knockout effects on sorafenib response, growth, and motility in hepatocellular carcinoma cell models

Article Title: NHSL3 knockout modulates sorafenib response, growth, and motility in hepatocellular carcinoma cell models

Article References: Yıldız, G., Karabulut, S., & Dinçer, T. (2026). NHSL3 knockout modulates sorafenib response, growth, and motility in hepatocellular carcinoma cell models. Molecular Biology Reports, 53(1), Article 1591. https://doi.org/10.1007/s11033-026-12760-4

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12760-4

Keywords: NHSL3, hepatocellular carcinoma, sorafenib, Huh-7 cells, Hep3B cells, cell models, cancer cell biology, migration, clonogenic growth, knockout, modulates, response