【NATURE】肝细胞癌的新发现：甲状腺激素可通过诱导癌症干细胞的自我复制来导致癌症的发生
2016-05-25来源：未知
【NATURE】肝细胞癌：甲状腺激素可通过诱导癌症干细胞的自我复制来导致癌症的发生
【NATURE】Hepatocellular carcinoma: thyroid hormonepromotes tumorigenicity through inducing cancer stem-like cell self-renewal
ScientificReports 6, Article number: 25183 (2016)
doi:10.1038/srep25183
Publishedonline: 12 May 2016
【关键字】癌症干细胞，胃肠道肿瘤
【摘要】
癌症干细胞或称癌干细胞（CSCs），在保持肝细胞癌（HCC）的侵袭性中发挥了关键作用，但是关于癌症干细胞的细胞生物学调节问题还不清楚。本次研究报道了，甲状腺激素（TH）会促进肝癌细胞的自我复制。该过程同时增加了CD90 + 肝癌细胞的比例，提高了肝癌细胞的耐药性。通过分析原发性肝癌样本，研究发现，相较于邻近的正常肝组织，在原发性肝癌和门静脉转移瘤中，TRα的转录水平出现明显升高。敲除TRα不仅能抑制体外肝癌细胞的自我复制，而且还能抑制体内肝癌细胞的生长。有趣的是，改变甲状腺激素水平会可激活NF-κB，而NF-κB正是利用了甲状腺激素的作用才诱导了肝癌细胞的自我复制。研究还发现TRα和p65通过共同结合基因BMI1的启动子区来合作驱动了BMI1的表达。总之，此次研究揭示了，甲状腺激素的信号转导在调控肝癌细胞的癌症干细胞上的一个新功能，而通过利用甲状腺激素对肝癌细胞的这一功能，这些发现可能会对开发肝癌细胞新疗法有用。
Cancerstem-like cells (CSCs) play a key role in maintaining the aggressiveness ofhepatocellular carcinoma (HCC), but the cell-biological regulation of CSCs isunclear. In the study, we report that thyroid hormone (TH) promotes cellself-renewal in HCC cells. TH also increases the percentage of CD90 + HCC cellsand promotes drug resistance of HCC cells. By analyzing primary human HCCsamples, we found that TRα transcript level is significantly elevated inprimary liver cancer and portal vein metastatic tumor, compared to that ofadjacent 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 andp65 cooperatively drive the expression of BMI1 by co-binding to the promoterregion of BMI1 gene. In summary, our study uncovers a novel function of THsignaling in regulating the CSCs of HCC, and these findings might be useful fordeveloping novel therapies by targeting TH function in HCC cells.
【NATURE】Hepatocellular carcinoma: thyroid hormonepromotes tumorigenicity through inducing cancer stem-like cell self-renewal
ScientificReports 6, Article number: 25183 (2016)
doi:10.1038/srep25183
Publishedonline: 12 May 2016
【关键字】癌症干细胞，胃肠道肿瘤
【摘要】
癌症干细胞或称癌干细胞（CSCs），在保持肝细胞癌（HCC）的侵袭性中发挥了关键作用，但是关于癌症干细胞的细胞生物学调节问题还不清楚。本次研究报道了，甲状腺激素（TH）会促进肝癌细胞的自我复制。该过程同时增加了CD90 + 肝癌细胞的比例，提高了肝癌细胞的耐药性。通过分析原发性肝癌样本，研究发现，相较于邻近的正常肝组织，在原发性肝癌和门静脉转移瘤中，TRα的转录水平出现明显升高。敲除TRα不仅能抑制体外肝癌细胞的自我复制，而且还能抑制体内肝癌细胞的生长。有趣的是，改变甲状腺激素水平会可激活NF-κB，而NF-κB正是利用了甲状腺激素的作用才诱导了肝癌细胞的自我复制。研究还发现TRα和p65通过共同结合基因BMI1的启动子区来合作驱动了BMI1的表达。总之，此次研究揭示了，甲状腺激素的信号转导在调控肝癌细胞的癌症干细胞上的一个新功能，而通过利用甲状腺激素对肝癌细胞的这一功能，这些发现可能会对开发肝癌细胞新疗法有用。
Cancerstem-like cells (CSCs) play a key role in maintaining the aggressiveness ofhepatocellular carcinoma (HCC), but the cell-biological regulation of CSCs isunclear. In the study, we report that thyroid hormone (TH) promotes cellself-renewal in HCC cells. TH also increases the percentage of CD90 + HCC cellsand promotes drug resistance of HCC cells. By analyzing primary human HCCsamples, we found that TRα transcript level is significantly elevated inprimary liver cancer and portal vein metastatic tumor, compared to that ofadjacent 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 andp65 cooperatively drive the expression of BMI1 by co-binding to the promoterregion of BMI1 gene. In summary, our study uncovers a novel function of THsignaling in regulating the CSCs of HCC, and these findings might be useful fordeveloping novel therapies by targeting TH function in HCC cells.
