Aberrant hedgehog signaling is responsible for the highly invasive behavior of a subpopulation of hepatoma cells

Oncogene
Y-H FanJ Wu

Abstract

Hepatoma exhibits a series of heterogeneous subpopulations in its cell surface markers, tumorigenicity, invasion and metastatic capability. We previously demonstrated that the CD133(-)/EpCAM(-) hepatoma subpopulation was more metastatic than its counterpart; however, the controlling mechanisms are unexplored. The present study aimed to delineate the significance of aberrant hedgehog (Hh) signaling in the mediation of metastases. Fluorescence-activated cell sorting-enriched CD133(-)/EpCAM(-) (double negative, DN), Huh-7 cells underwent a transwell selection for metastatic cells (transwell-selected, TS). The TS cells displayed much greater metastatic activity as evidenced by an increased invasion rate, extremely upregulated expression of matrix metalloproteinase (MMP)-1/2/9 genes compared with DN and double-positive (DP) subpopulations. In contrast to DP cells, TS cells lost E-cadherin and were all vimentin-positive as shown by immunocytochemistry. There was a transitional increase in Gli-1/2 gene expression levels from DP, DN to TS subpopulations, which was consistent with elevated Gli-1/2 or Twist-1 protein levels in the nuclear fraction. Furthermore, truncated Gli-1 (tGli-1), which transactivates molecules involved in metastas...Continue Reading

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Citations

Jun 22, 2016·Journal of Agricultural and Food Chemistry·Cheng BaoHong Jin Lee
Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Richard L Carpenter, Haimanti Ray
Feb 29, 2020·Journal of Cellular and Molecular Medicine·Xiao-Tian ZhouJian Wu
Mar 1, 2017·Stem Cells International·Ana Almazán-MogaSoledad Gallego
Sep 5, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Gang XuJian Wu
Sep 23, 2020·Cells·Daniel DohenyHui-Wen Lo
Apr 18, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jia DingJian Wu
Jan 30, 2020·Journal of Experimental & Clinical Cancer Research : CR·Siqi WangJiye Zhu

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