Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells.

  title={Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells.},
  author={Chia-Lin Chen and Hidekazu Tsukamoto and J Liu and Claudine Kashiwabara and Douglas Edmund Feldman and Linda Sher and Steven Dooley and Samuel William French and Lopa Mishra and Lydia M. Petrovic and Joseph Jeong and Keigo Machida},
  journal={The Journal of clinical investigation},
  volume={123 7},
Tumor-initiating stem-like cells (TICs) are resistant to chemotherapy and associated with hepatocellular carcinoma (HCC) caused by HCV and/or alcohol-related chronic liver injury. Using HCV Tg mouse models and patients with HCC, we isolated CD133(+) TICs and identified the pluripotency marker NANOG as a direct target of TLR4, which drives the tumor-initiating activity of TICs. These TLR4/NANOG-dependent TICs were defective in the TGF-β tumor suppressor pathway. Functional oncogene screening of… CONTINUE READING
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