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Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma

  • Authors:
    • Jared E. Limones‑Gonzalez
    • Perla Aguilar Esquivel
    • Karla Vazquez-Santillan
    • Rosario Castro-Oropeza
    • Floria Lizarraga
    • Vilma Maldonado
    • Jorge Melendez‑Zajgla
    • Patricia Piña-Sanchez
    • Gretel Mendoza‑Almanza
  • View Affiliations / Copyright

    Affiliations: Biotechnology Laboratory, Autonomous University of Zacatecas, Zacatecas 98160, Mexico, Department of Pathology, Zacatecas General Hospital Luz González Cosío, Zacatecas 98160, Mexico, Innovation in Precision Medicine Laboratory, National Institute of Genomic Medicine, Mexico City 14610, Mexico, Molecular Oncology Laboratory, Oncology Research Unit, XXI Century National Medical Center, IMSS, Mexico City 06720, Mexico, Epigenetics Laboratory, National Institute of Genomic Medicine, Mexico City 14610, Mexico, Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine, Mexico City 14610, Mexico
    Copyright: © Limones‑Gonzalez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 522
    |
    Published online on: August 30, 2024
       https://doi.org/10.3892/ol.2024.14655
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Abstract

Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes‑associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular‑MYC, cAMP response element‑binding binding protein (CREBBP), E1A‑associated cellular p300 transcriptional co‑activator protein and F‑Box and WD repeat domain containing 7] and the nuclear factor erythroid 2‑related factor 2 (NRF2) pathway [NRF2, kelch‑like ECH‑associated protein 1 (KEAP1), AKT and PIK3‑catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription‑quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c‑MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c‑MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer‑free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.
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Copy and paste a formatted citation
Spandidos Publications style
Limones‑Gonzalez JE, Aguilar Esquivel P, Vazquez-Santillan K, Castro-Oropeza R, Lizarraga F, Maldonado V, Melendez‑Zajgla J, Piña-Sanchez P and Mendoza‑Almanza G: Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma. Oncol Lett 28: 522, 2024.
APA
Limones‑Gonzalez, J.E., Aguilar Esquivel, P., Vazquez-Santillan, K., Castro-Oropeza, R., Lizarraga, F., Maldonado, V. ... Mendoza‑Almanza, G. (2024). Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma. Oncology Letters, 28, 522. https://doi.org/10.3892/ol.2024.14655
MLA
Limones‑Gonzalez, J. E., Aguilar Esquivel, P., Vazquez-Santillan, K., Castro-Oropeza, R., Lizarraga, F., Maldonado, V., Melendez‑Zajgla, J., Piña-Sanchez, P., Mendoza‑Almanza, G."Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma". Oncology Letters 28.5 (2024): 522.
Chicago
Limones‑Gonzalez, J. E., Aguilar Esquivel, P., Vazquez-Santillan, K., Castro-Oropeza, R., Lizarraga, F., Maldonado, V., Melendez‑Zajgla, J., Piña-Sanchez, P., Mendoza‑Almanza, G."Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma". Oncology Letters 28, no. 5 (2024): 522. https://doi.org/10.3892/ol.2024.14655
Copy and paste a formatted citation
x
Spandidos Publications style
Limones‑Gonzalez JE, Aguilar Esquivel P, Vazquez-Santillan K, Castro-Oropeza R, Lizarraga F, Maldonado V, Melendez‑Zajgla J, Piña-Sanchez P and Mendoza‑Almanza G: Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma. Oncol Lett 28: 522, 2024.
APA
Limones‑Gonzalez, J.E., Aguilar Esquivel, P., Vazquez-Santillan, K., Castro-Oropeza, R., Lizarraga, F., Maldonado, V. ... Mendoza‑Almanza, G. (2024). Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma. Oncology Letters, 28, 522. https://doi.org/10.3892/ol.2024.14655
MLA
Limones‑Gonzalez, J. E., Aguilar Esquivel, P., Vazquez-Santillan, K., Castro-Oropeza, R., Lizarraga, F., Maldonado, V., Melendez‑Zajgla, J., Piña-Sanchez, P., Mendoza‑Almanza, G."Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma". Oncology Letters 28.5 (2024): 522.
Chicago
Limones‑Gonzalez, J. E., Aguilar Esquivel, P., Vazquez-Santillan, K., Castro-Oropeza, R., Lizarraga, F., Maldonado, V., Melendez‑Zajgla, J., Piña-Sanchez, P., Mendoza‑Almanza, G."Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma". Oncology Letters 28, no. 5 (2024): 522. https://doi.org/10.3892/ol.2024.14655
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