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Open AccessArticle

Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma

1
Cancer Biology Laboratory & DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
2
Department of Biotechnology, Mizoram University, Aizawl 796 004, Mizoram, India
3
North-East Cancer Hospital and Research Institute, Guwahati 781023, Assam, India
4
Stem Cell and Cancer Biology Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6009, Australia
5
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
6
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
7
Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
8
Medical School, Faculty of Health Sciences, Curtin University, Perth, WA 6845, Australia
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(7), 253; https://doi.org/10.3390/biom9070253
Received: 14 March 2019 / Revised: 5 June 2019 / Accepted: 22 June 2019 / Published: 27 June 2019
(This article belongs to the Special Issue Antitumor Agents from Natural Sources)
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 “The Cancer Genome Atlas” 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. View Full-Text
Keywords: Akt isoforms; oral cancer; tissue microarray; immunohistochemistry; tobacco; knockdown Akt isoforms; oral cancer; tissue microarray; immunohistochemistry; tobacco; knockdown
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Figure 1

MDPI and ACS Style

Roy, N.K.; Monisha, J.; Padmavathi, G.; Lalhruaitluanga, H.; Kumar, N.S.; Singh, A.K.; Bordoloi, D.; Baruah, M.N.; Ahmed, G.N.; Longkumar, I.; Arfuso, F.; Kumar, A.P.; Kunnumakkara, A.B. Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma. Biomolecules 2019, 9, 253.

AMA Style

Roy NK, Monisha J, Padmavathi G, Lalhruaitluanga H, Kumar NS, Singh AK, Bordoloi D, Baruah MN, Ahmed GN, Longkumar I, Arfuso F, Kumar AP, Kunnumakkara AB. Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma. Biomolecules. 2019; 9(7):253.

Chicago/Turabian Style

Roy, Nand K.; Monisha, Javadi; Padmavathi, Ganesan; Lalhruaitluanga, H.; Kumar, Nachimuthu S.; Singh, Anuj K.; Bordoloi, Devivasha; Baruah, Munindra N.; Ahmed, Gazi N.; Longkumar, Imliwati; Arfuso, Frank; Kumar, Alan P.; Kunnumakkara, Ajaikumar B. 2019. "Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma" Biomolecules 9, no. 7: 253.

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