Single-cell transcriptomic profiling reveals that KLF2 limits tumor cell plasticity in hepatocellular carcinoma

In epithelial-derived liver cancer, epithelial-mesenchymal plasticity (EMP), including epithelial-mesenchymal transition (EMT) and partial EMT (pEMT) programs, is considered a key driver of tumor progression, therapeutic resistance, recurrence, and metastasis. KLF2 has been suggested to function as a tumor suppressor in liver cancer, but its role in regulating tumor cell plasticity in HCC remains incompletely understood.

To address this question, we established a c-MYC/AKT-driven murine HCC model with or without KLF2 overexpression and performed single-cell RNA sequencing on tumor tissues. Mouse HCC was induced by hydrodynamic tail vein injection of pT3-EF1α-c-MYC and pT3-EF1α-AKT plasmids together with the SB100X transposase plasmid, and liver tumors developed 10 weeks after injection. In the KLF2 overexpression group, pT3-EF1α-KLF2 was additionally co-injected.