Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
Background: The AKT/PKB (protein kinase B) kinase is the main regulator of autophagy in mammalian cells, which consists of three isoforms, including AKT-1, AKT-2, and AKT-3. Rat sarcoma viral oncogene homolog (RAS), known as the most frequently mutated oncogene in colorectal cancers, is one of the m...
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| Autores principales: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Shiraz University of Medical Sciences
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/76fdd070a5904d649ed9b484e1c92863 |
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| Sumario: | Background: The AKT/PKB (protein kinase B) kinase is the main regulator of autophagy in mammalian cells, which consists of three isoforms, including AKT-1, AKT-2, and AKT-3. Rat sarcoma viral oncogene homolog (RAS), known as the most frequently mutated oncogene in colorectal cancers, is one of the major activators of AKT signaling. However, the relationship between AKT isoforms expression and autophagy level in RAS-driven cancer cells has not been fully investigated. Method: In this experimental in vitro study, RAS mutated colon cancer cell lines (HCT116, SW480, and LS180) and HT29 cells, which are the wild type of RAS, were cultured and real-time polymerase chain reaction (RT-PCR) was utilized to determine the mRNA level of AKT-1, AKT-2, and autophagy markers, including microtubule-associated protein 1 light chain-3B (LC3B) and p62/sequestosome-1 (p62). In addition, Western blotting was performed to assess the protein expression of p62 and LC3B lipidation. Results: We found that RAS mutated colon cancer cells up-regulate basal autophagy. Moreover, highly expressed AKT-1 was observed in RAS mutated colon cancer cells. However, no significant differences were found in AKT-2 expression between RASdriven cells and HT29 cells. Conclusion: Our obtained data suggested that RAS-driven colon cancer cells regulated the autophagy machinery, possibly, through the upregulation of AKT-1 isoform. |
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