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:	Hamid Behrouj, Amir Mahmoudzadeh, Saeid Ghavami, Pooneh Mokarram
Formato:	article
Lenguaje:	EN
Publicado:	Shiraz University of Medical Sciences 2021
Materias:	colorectal neoplasms ras oncogenes autophagy akt/pkb kinase Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/76fdd070a5904d649ed9b484e1c92863
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spelling	oai:doaj.org-article:76fdd070a5904d649ed9b484e1c928632021-11-29T10:40:47ZAutophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells2008-67092008-668710.30476/mejc.2021.85836.1307https://doaj.org/article/76fdd070a5904d649ed9b484e1c928632021-10-01T00:00:00Zhttps://mejc.sums.ac.ir/article_47355_647668358921b91f30b9b2e5771bf4a5.pdfhttps://doaj.org/toc/2008-6709https://doaj.org/toc/2008-6687Background: 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.Hamid BehroujAmir MahmoudzadehSaeid GhavamiPooneh MokarramShiraz University of Medical Sciencesarticlecolorectal neoplasmsrasoncogenesautophagyakt/pkb kinaseNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMiddle East Journal of Cancer , Vol 12, Iss 4, Pp 457-465 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal neoplasms ras oncogenes autophagy akt/pkb kinase Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal neoplasms ras oncogenes autophagy akt/pkb kinase Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hamid Behrouj Amir Mahmoudzadeh Saeid Ghavami Pooneh Mokarram Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
description	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.
format	article
author	Hamid Behrouj Amir Mahmoudzadeh Saeid Ghavami Pooneh Mokarram
author_facet	Hamid Behrouj Amir Mahmoudzadeh Saeid Ghavami Pooneh Mokarram
author_sort	Hamid Behrouj
title	Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
title_short	Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
title_full	Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
title_fullStr	Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
title_full_unstemmed	Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells
title_sort	autophagy flux correlates with upregulation of akt-1 in ras mutated colon cancer cells
publisher	Shiraz University of Medical Sciences
publishDate	2021
url	https://doaj.org/article/76fdd070a5904d649ed9b484e1c92863
work_keys_str_mv	AT hamidbehrouj autophagyfluxcorrelateswithupregulationofakt1inrasmutatedcoloncancercells AT amirmahmoudzadeh autophagyfluxcorrelateswithupregulationofakt1inrasmutatedcoloncancercells AT saeidghavami autophagyfluxcorrelateswithupregulationofakt1inrasmutatedcoloncancercells AT poonehmokarram autophagyfluxcorrelateswithupregulationofakt1inrasmutatedcoloncancercells
_version_	1718407409212325888

Autophagy Flux Correlates with Upregulation of AKT-1 in RAS Mutated Colon Cancer Cells

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