Hepatocellular carcinoma (HCC), the most common liver cancer, is the third leading cause of cancer related death. A subset of cells with stem/progenitor cell features known as cancer stem cells (CSCs), accounting for tumor initiation, metastasis, drug resistance and recurrence, emerge as a potential target for tumor eradication. However, the molecular mechanisms to sustain liver CSCs remain largely unknown.
To search for driver genes in the oncogenesis of HCC and self-renewal maintenance of liver CSCs, researchers from FAN Zusen's lab at the Institute of Biophysics (IBP) of Chinese Academy of Sciences performed genome-wide analyses using several online-available HCC transcriptome datasets.
The researchers found C8orf4 was weakly expressed in liver cancer cells, liver stem cells and liver CSCs. Sphere formation and xenograft formation confirmed that C8orf4 inhibits the self-renewal of liver CSCs. Moreover, C8orf4 interacts with Notch2 intracellular domain (N2ICD), blocks its nuclear translocation, and finally inhibits Notch signaling.
Notch2 signaling activation is well correlated with severity and prognosis of HCC patients. Thus, targeting Notch2 signaling might be used to eradicate liver CSCs for future therapy.
This study was published on Nature Communications entitled “C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signaling”.
Figure: A working model on the regulation of Liver CSC self-renewal by C8orf4. (Image by IBP)
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