Authors
Ramjan Sheikh, Punam Chowdhury, Ekhlas Uddin, Jarin Tasnim, Mobin Mahmud Shawon, Sohela Faisal, Abu Sayed, M Salahuddin, Abrar Farhan Fuad
Published in
Oncotarget. Volume 17. Issue 1. Pages 437-461. Oct 12, 2026.
Abstract
Copyright: © 2026 Sheikh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. AKT1 is a serine-threonine protein-kinase involved in tumour cell proliferation, survival, metabolism, and therapeutic resistance via activation of the PI3K/AKT/mTOR pathway. However, the comprehensive pan-cancer characterization of AKT1 and systematics identifications of natural AKT1 inhibitors remains limited. This study comprehensively evaluated the expression patterns and mutation landscape of AKT1, its promoter methylation, immune infiltration, and clinical significance using the TCGA datasets for 33 cancer types. AKT1 showed significant over-expression in BRCA, HNSC, CHOL, STAD, and UCEC while being under-expressed in PRAD and GBM. Survival analysis demonstrated cancer-specific prognostic associations of AKT1 expression, and cBioPortal profiling characterized E17 as having hotspot missense mutations. Promoter methylation profiling revealed widespread hypomethylation that correlates with increased transcription. AKT1 was widely expressed in normal tissues, and its localization was mainly cytoplasmic, varying according to cell type. At the single cell level, expression was detected in malignant, immune, and stromal compartments. AKT1 expression exhibited tumor-specific associations with tumor mutational burden and microsatellite instability. To identify candidate natural inhibitors, this study computationally screened 52 buckwheat-derived phytochemicals with AKT1. Fagopyrine showed the strongest binding affinity (−15.45 kcal/mol) and remained structurally stable and flexible with AKT1 protein at 100 ns MD simulation. ADMET and DFT analyses indicated favorable electronic stability but predicted moderate gastrointestinal absorption, suggesting that further structural optimization is required. In summary, this study reveals that fagopyrine is a promising computational AKT1 targeting lead, but the direct biochemical and cancer cell-line validation experiments required to confirm its AKT1 inhibitory activity and anticancer efficacy remain to be performed.
PMID:
42862713
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 2
- Comments 0