AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1
| Autor: | Haoran Li, Zhengrong Zhang, Junfeng Wang, Menglin Xu, Zhengwu Cheng |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Aging Colorectal cancer Gli1 AIM2 migration Metastasis Mice Cell Movement Enzyme Inhibitors biology TOR Serine-Threonine Kinases Middle Aged DNA-Binding Proteins Gene Knockdown Techniques Lymphatic Metastasis Female Signal transduction Colorectal Neoplasms Signal Transduction Research Paper Epithelial-Mesenchymal Transition Morpholines proliferation Mice Nude colorectal cancer Adenocarcinoma Zinc Finger Protein GLI1 GLI1 Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness neoplasms Protein kinase B Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Aged Cell Proliferation Neoplasm Staging Cell growth Cell Biology HCT116 Cells medicine.disease digestive system diseases Chromones biology.protein Cancer research Proto-Oncogene Proteins c-akt Neoplasm Transplantation |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Colorectal cancer (CRC) is a common malignant tumor and is one of the leading causes of cancer-related deaths worldwide. Absent in melanoma 2 (AIM2), as a member of the pyrin-HIN family proteins, plays contentious roles in different types of cancers. In the present work, we provide evidence that AIM2 was commonly downregulated in human CRC and loss of AIM2 significantly correlated with tumor size, depth of invasion, lymph node metastasis (LNM) and TNM (Tumor, Node, Metastases) stage in patients suffering from CRC. AIM2 knockdown promoted CRC cell proliferation, migration and epithelial-mesenchymal transition (EMT) progress, whereas AIM2 overexpression did the opposite. AIM2 inhibited glioma-associated oncogene-1 (Gli1) expression through Smoothened homolog (SMO)-independent pathway and regulated CRC cell proliferation and migration in a Gli1-dependent manner. Moreover, AIM2 could modulate Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway and the increased Gli1 expression and EMT progress induced by AIM2 depletion was reversed after incubation with AKT inhibitor Ly294002 in CRC cells. In conclusion, our results define AIM2 as a novel regulator of Gli1 in CRC cell growth and metastasis, and suggest that the AIM2/AKT/mTOR/Gli1 signaling axis may serve as a potential target for treatment of CRC. |
| Databáze: | OpenAIRE |
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