Accession Number : AD1017719


Title :   The Role of Akt Isoforms in Colorectal Cancer


Descriptive Note : Technical Report,01 Jul 2013,30 Jun 2015


Corporate Author : Tufts Medical Center Inc Boston United States


Personal Author(s) : Roper,Jatin


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1017719.pdf


Report Date : 01 Sep 2015


Pagination or Media Count : 9


Abstract : Akt activation is found in many cancers, including CRC, and is a marker for CRC initiation and progression. However, since Akt has a central role in cell signaling, targeting the three Akt isoforms concurrently may give rise to unacceptable toxicity. Therefore, selective inhibition of one or more Akt isoforms or their target phosphoproteins may be a more effective treatment strategy for CRC. Though a phosphoproteomics screen, we identified 20 Akt isoform-specific phosphorylation targets as likely to be involved in tumor growth and metastasis. We hypothesized that Akt isoforms and their downstream effectors play essential roles in CRC induction, growth and metastasis. We have found that knockout of Akt1 or Akt2 substantially reduces colorectal tumorigenesis in our genetically engineered mouse model. We also successfully ablated novel downstream targets of Akt in our novel murine colorectal cancer cell lines: IWS1, MTSS1 or MIM, FRMD6, SEMA4B, MYH9, and Liprin-1. We found that each phosphorylation target promotes tumorngenesis in vitro. MTSS1 had the greatest effect on in vitro tumorigenesis.


Descriptors :   cancer , Oncogenesis , neoplasms , phosphorylation , mucous membrane , mutant proteins , therapeutics , tumor cell line , antibodies , inhibition , suppressors , biomedical research


Distribution Statement : APPROVED FOR PUBLIC RELEASE