| 研究実績の概要 |
Recently, we demonstrated critical role of EPS8L3 (epidermal growth factor receptor kinase substrate 8-like protein 3) in cholangiocarcinoma (CCA), a deadly form of liver cancer. The EPS8 family, including EPS-like (EPS8L) 1, EPS8L2, and EPS8L3, plays an important role in a wide variety of cancers.
Elevated expression of the EPS8L3 gene was validated using RNA-seq data from TCGA (The Cancer Genome Atlas) database, showing that EPS8L3 was overexpressed in CCAs (n=36) relative to normal bile duct tissue (n=9), and HCCs (n=373) relative to normal liver tissue (n=50). In addition, EPS8L3 was overexpressed 19- to 1160- fold in 10 liver tumors, when compared with paired normal liver tissue. Besides, EPS8L3 overexpression was also found in a panel of CCA cell lines (n=4) and hepatocellular carcinoma (HCC) cell lines (n=2) compared with human bile duct cell line (MMNK1) and human hepatocyte cell line (Hc3716).
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| 今後の研究の推進方策 |
We will overexpress EPS8L3 in normal bile duct cells (MMNK1 and H69 cells) and CCA cells with weak EPS8L3 expression. In addition, to confirm the role of EPS8L3 in regulating malignant behaviors of CCA cells, we will use EPS8L3 siRNA to knock down EPS8L3 in CCA cell lines (HuCTT1, RBE and KMCH); then examine the cell growth, mammosphere formation, apoptosis, cell cycle, migration and invasion ability, and the epithelial-mesenchymal transition (EMT) using a three-dimentional culture model. Besides, we will clarify the molecular mechanisms using real time PCR, Western blotting, immunohistochemistry and immunofluorescent staining.
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