The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 11 - 2024 |
doi: 10.3389/fmolb.2024.1386930
This article is part of the Research Topic Tumor-host interactions: metabolic and signaling pathways altered in cancer, immune and stromal cells View all 3 articles
Dynamics Simulations of Hypoxia Inducible Factor-1(HIF-1) Regulatory Network in Cancer Using Formal Verification Techniques
Provisionally accepted- National University of Sciences and Technology (NUST), Islamabad, Islamabad, Pakistan
Hypoxia-inducible factor-1 (HIF-1) regulates cell growth, protein translation, metabolic pathways and therefore, has been advocated as a promising biological target for the therapeutic interventions against cancer. In general, hyperactivation of HIF-1 in cancer has been associated with increases in the expression of glucose transporter type-1 (GLUT-1) thus, enhancing glucose consumption and hyperactivating metabolic pathways. The collective behavior of GLUT-1 along with previously known key players AKT, OGT, and VEGF is not fully characterized and lacks clarity of how glucose uptake through this pathway (HIF-1) probes the cancer progression. This study uses a Rene Thomas qualitative modeling framework to comprehend the signaling dynamics of HIF-1 and its interlinked proteins, including VEGF, ERK, AKT, GLUT-1, β-catenin, C-MYC, OGT, and p53 to elucidate the regulatory mechanistic of HIF-1 in cancer. Our dynamic model reveals that continuous activation of p53, β-catenin, and AKT in cyclic conditions, leads to oscillations representing homeostasis or a stable recovery state. Any deviation from this cycle results in a cancerous or pathogenic state. The model shows that overexpression of VEGF activates ERK and GLUT-1, leads to more aggressive tumor growth in a cancerous state. Moreover, it is observed that collective modulation of VEGF, ERK, and β-catenin is required for therapeutic intervention because these genes enhance the expression of GLUT-1 and play a significant role in cancer progression and angiogenesis. Additionally, SimBiology simulation unveils dynamic molecular interactions, emphasizing the need for targeted therapeutics to effectively regulate VEGF and ERK concentrations to modulate cancer cell proliferation.
Keywords: Hypoxia-inducible factor-1 (HIF-1), Vascular endothelial growth factor(VEGF), Oglycosylation transferase(OGT), Glucose transporter-1(GLUT-1), Extracellular single regulated kinase(ERK), Cellular myelocytomatosis oncogene(C-MYC) Comment [M8]: Details added Comment [M9]: Comment [M10]: Comment [M11]: Comment [M12]:
Received: 16 Feb 2024; Accepted: 28 Oct 2024.
Copyright: © 2024 Azhar, Jabeen and Saeed. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ishrat Jabeen, National University of Sciences and Technology (NUST), Islamabad, 44000, Islamabad, Pakistan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.