title: Hepatocellular carcinoma: thyroid hormone promotes tumorigenicity through inducing cancer stem-like cell self-renewal.
abstract: Cancer stem-like cells (CSCs) play a key role in maintaining the aggressiveness of hepatocellular carcinoma (HCC), but the cell-biological regulation of CSCs is unclear. In the study, we report that thyroid hormone (TH) promotes cell self-renewal in HCC cells. TH also increases the percentage of CD90 + HCC cells and promotes drug resistance of HCC cells. By analyzing primary human HCC samples, we found that TRα transcript level is significantly elevated in primary liver cancer and portal vein metastatic tumor, compared to that of adjacent normal liver tissue. Knocking down TRα not only inhibits HCC self-renewal in vitro but also suppresses HCC tumor growth in vivo. Interestingly, treatment of TH leads to activation of NF-κB, which is required for the function of TH on inducing HCC cell self-renewal. We also found TRα and p65 cooperatively drive the expression of BMI1 by co-binding to the promoter region of BMI1 gene. In summary, our study uncovers a novel function of TH signaling in regulating the CSCs of HCC, and these findings might be useful for developing novel therapies by targeting TH function in HCC cells.
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Hepatic surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Sicong
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Hepatic surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Qigen
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hepatic surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Dan
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Jiachang
authors.initials: J
authors.lastname: Chi
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Yu-Xiong
authors.initials: YX
authors.lastname: Feng
authors.affiliation: Department of Hepatic surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PRC, 200127.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhai
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D000066673:Cell Self Renewal / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones