Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling
| Autor: | Lidong Wang, Lirong Zhang, Yingge Liu, Mingzhou Guo, Meiying Zhang, Tao He, Weili Yang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Esophageal Neoplasms medicine.medical_treatment Cell Esophageal cancer Biology Decitabine Epigenesis Genetic Mice Phosphatidylinositol 3-Kinases Cell Line Tumor Genetics medicine Animals Humans Gene Silencing Enzyme Inhibitors Molecular Biology Genetics (clinical) Aged Neoplasm Staging Aged 80 and over DNA methylation Cell growth PI3K-AKT Growth factor Tumor Suppressor Proteins Research IGFBPL1 Methylation Middle Aged medicine.disease Insulin-Like Growth Factor Binding Proteins medicine.anatomical_structure Cell culture Apoptosis Models Animal Cancer research Heterografts Female Esophageal Squamous Cell Carcinoma Proto-Oncogene Proteins c-akt Developmental Biology Signal Transduction |
| Zdroj: | Clinical Epigenetics |
| ISSN: | 1868-7083 |
| Popis: | Background There are seven insulin-like growth factor binding proteins (IGFBPs) that bind insulin-like growth factors (IGFs). IGFBP like protein1 (IGFBPL1) is a new member of this family. The function and mechanism of IGFBPL1 in esophageal cancer remains to be elucidated. Methods Eight esophageal cancer cell lines, 114 cases of esophageal dysplasia, and 501 cases of primary esophageal cancer samples were examined in this study. Methylation-specific polymerase chain reaction (MSP), immunohistochemistry, Western blot, flow cytometry, RNA interference assay, and xenograft mouse models were employed. Results The expression of IGFBPL1was lost and complete methylation was found in KYSE150 and KYSE410 cells. Reduced expression and partial methylation of IGFBPL1 was found in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells. High expression and unmethylation was detected in KYSE510 cells. Restoration of IGFBPL1 expression was found in KYSE150 and KYSE410 cells and the expression of IGFBPL1 was increased in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells, after 5-AZA-2′-deoxycytidine treatment. IGFBPL1 was methylated in 47.3% (53/114) of esophageal dysplasia and 49.1% (246/501) of human primary esophageal squamous cell carcinoma (ESCC). Methylation of IGFBPL1 was significantly associated with TNM stage (p = 0.012), and tumor size (p = 0.009). IGFBPL1 inhibited esophageal cancer cell clonal formation and proliferation and induced cell apoptosis and G1/S phase arrest. Further study found that IGFBPL1 is involved in PI3K-AKT signaling and IGFBPL1 suppressed human ESCC xenografts growth in mice. Conclusion IGFBPL1 suppresses esophageal cancer cell growth by inhibiting PI3K-AKT signaling in vitro and in vivo. IGFBPL1 is a novel tumor suppressor in human esophageal cancer. |
| Databáze: | OpenAIRE |
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