XIdentification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling

Guobin He, Debanjan Dhar, Hayato Nakagawa, Joan Font-Burgada, Hisanobu Ogata, Yuhong Jiang, Shabnam Shalapour, Ekihiro Seki, Shawn E. Yost, Kristen Jepsen, Kelly A. Frazer, Olivier Harismendy, Maria Hatziapostolou, Dimitrios Iliopoulos, Atsushi Suetsugu, Robert M. Hoffman, Ryosuke Tateishi, Kazuhiko Koike, Michael Karin

Research output: Contribution to journalArticlepeer-review

358 Citations (Scopus)


Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to evolve from premalignant lesions in chronically damaged livers. However, it was never established that premalignant lesions actually contain tumor progenitors that give rise to cancer. Here, we describe isolation and characterization of HCC progenitor cells (HcPCs) from different mouse HCC models. Unlike fully malignant HCC, HcPCs give rise to cancer only when introduced into a liver undergoing chronic damage and compensatory proliferation. Although HcPCs exhibit a similar transcriptomic profile to bipotential hepatobiliary progenitors, the latter do not give rise to tumors. Cells resembling HcPCs reside within dysplastic lesions that appear several months before HCC nodules. Unlike early hepatocarcinogenesis, which depends on paracrine IL-6 production by inflammatory cells, due to upregulation of LIN28 expression, HcPCs had acquired autocrine IL-6 signaling that stimulates their in vivo growth and malignant progression. This may be a general mechanism that drives other IL-6-producing malignancies.

Original languageEnglish
Pages (from-to)384
Number of pages1
Issue number2
Publication statusPublished - Oct 10 2013

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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