Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma
Autor: | H. Lalhruaitluanga, Ajaikumar B. Kunnumakkara, Nand Kishor Roy, Javadi Monisha, Imliwati Longkumar, Gazi Naseem Ahmed, Devivasha Bordoloi, Anuj Kumar Singh, Nachimuthu Senthil Kumar, Frank Arfuso, Ganesan Padmavathi, Munindra Narayan Baruah, Alan Prem Kumar |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Nicotine Cell Survival lcsh:QR1-502 AKT1 AKT2 Biology Biochemistry tobacco Article lcsh:Microbiology 03 medical and health sciences 0302 clinical medicine Cyclin D1 Akt isoforms Survivin Tumor Cells Cultured Gene silencing Humans Gene Silencing Clonogenic assay Molecular Biology Protein kinase B Cell Proliferation tissue microarray Cell Cycle knockdown Tobacco Products oral cancer Isoenzymes 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell embryonic structures immunohistochemistry Cancer research Carcinoma Squamous Cell Mouth Neoplasms Proto-Oncogene Proteins c-akt |
Zdroj: | Biomolecules, Vol 9, Iss 7, p 253 (2019) Biomolecules Volume 9 Issue 7 |
Popis: | Protein kinase B (Akt) plays a very significant role in various cancers including oral cancer. However, it has three isoforms (Akt1, Akt2, and Akt3) and they perform distinct functions and even play contrasting roles in different cancers. Therefore, it becomes essential to evaluate the isoform-specific role of Akt in oral cancer. In the present study, an attempt has been made to elucidate the isoform-specific role of Akt in oral cancer. The immunohistochemical analysis of oral cancer tissues showed an overexpression of Akt1 and 2 isoforms but not Akt3. Moreover, the dataset of &ldquo The Cancer Genome Atlas&rdquo for head and neck cancer has suggested the genetic alterations of Akt1 and 2 tend to be associated with the utmost poor clinical outcome in oral cancer. Further, treatment of oral cancer cells with tobacco and its components such as benzo(a)pyrene and nicotine caused increased mRNA levels of Akt1 and 2 isoforms and also enhanced the aggressiveness of oral cancer cells in terms of proliferation, and clonogenic and migration potential. Finally, silencing of Akt1 and 2 isoforms caused decreased cell survival and induced cell cycle arrest at the G2/M phase. Akt1/2 silencing also reduced tobacco-induced aggressiveness by decreasing the clonogenic and migration potential of oral cancer cells. Moreover, silencing of Akt1 and 2 isoforms was found to decrease the expression of proteins regulating cancer cell survival and proliferation such as cyclooxygenase-2, B-cell lymphoma 2 (Bcl-2), cyclin D1, and survivin. Thus, the important role of Akt1 and 2 isoforms have been elucidated in oral cancer with in-depth mechanistic analysis. |
Databáze: | OpenAIRE |
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