Autophagy Flux Correlates with Upregulation of AKT-۱ 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-۱, AKT-۲, and AKT-۳. 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 (HCT۱۱۶, SW۴۸۰, and LS۱۸۰) and HT۲۹ 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-۱, AKT-۲, and autophagy markers, including microtubule-associated protein ۱ light chain-۳B (LC۳B) and p۶۲/sequestosome-۱ (p۶۲). In addition, Western blotting was performed to assess the protein expression of p۶۲ and LC۳B lipidation. Results: We found that RAS mutated colon cancer cells up-regulate basal autophagy. Moreover, highly expressed AKT-۱ was observed in RAS mutated colon cancer cells. However, no significant differences were found in AKT-۲ expression between RASdriven cells and HT۲۹ cells. Conclusion: Our obtained data suggested that RAS-driven colon cancer cells regulated the autophagy machinery, possibly, through the upregulation of AKT-۱ isoform.

کلیدواژه ها:

Colorectal neoplasms ، Ras ، Oncogenes ، Autophagy ، AKT/PKB kinase