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المؤلفTherachiyil, Lubna
المؤلفKrishnankutty, Roopesh
المؤلفAhmad, Fareed
المؤلفMateo, Jericha M.
المؤلفUddin, Shahab
المؤلفKorashy, Hesham M.
تاريخ الإتاحة2023-10-11T09:58:58Z
تاريخ النشر2022-06-07
اسم المنشورInternational Journal of Molecular Sciences
المعرّفhttp://dx.doi.org/10.3390/ijms23126395
الاقتباسTherachiyil, L., Krishnankutty, R., Ahmad, F., Mateo, J. M., Uddin, S., & Korashy, H. M. (2022). Aryl hydrocarbon receptor promotes cell growth, stemness like characteristics, and metastasis in human ovarian cancer via activation of PI3K/Akt, β-catenin, and epithelial to mesenchymal transition pathways. International Journal of Molecular Sciences, 23(12), 6395.
الرقم المعياري الدولي للكتاب1661-6596
معرّف المصادر الموحدhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85131313887&origin=inward
معرّف المصادر الموحدhttp://hdl.handle.net/10576/48447
الملخصOvarian cancer (OC) ranks first in cancer-related deaths out of all female reproductive malignancies with high-pitched tumor relapse and chemoresistance. Several reports correlate cancer occurrences with exposure to xenobiotics via induction of a protein receptor named aryl hydrocarbon receptor (AhR). However, the effect of AhR on OC proliferation, expansion, and chemoresistance remains unrevealed. For this purpose, OC cells A2780 and A2780cis cells were treated with AhR activator, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the effects were determined by Real-Time Cell Analyzer, clonogenic assay, flow cytometry, immunoblotting and wound healing assay. Our results showed that activation of AhR by TCDD in A2780 cells induced the PI3K/AKT pathway followed by induction of anti-apoptotic proteins BCL-2, BCL-xl, and MCL-1. In addition, a significant increase in stemness marker aldehyde dehydrogenase (ALDH1) was observed. This effect was also associated with an accumulation of β-catenin, a Wnt transcription factor. Moreover, we observed induction of epithelial to mesenchymal transition (EMT) upon AhR activation. In conclusion, the results from the current study confirm that AhR mediates OC progression, stemness characteristics, and metastatic potential via activation of PI3K/Akt, Wnt/β-catenin, and EMT. This study provides a better insight into the modulatory role of AhR that might help in developing novel therapeutic strategies for OC treatment.
راعي المشروعFunding: This study was funded by the Medical Research center (MRC), Hamad Medical Corporation (MRC-01-21-820), Doha, Qatar, and Office of Research Support, Qatar University (QUST-1-CPH-2019-18), Doha, Qatar.
اللغةen
الناشرMultidisciplinary Digital Publishing Institute (MDPI)
الموضوعapoptosis
aryl hydrocarbon receptor
chemoresistance
EMT
ovarian cancer
stemness
العنوانAryl Hydrocarbon Receptor Promotes Cell Growth, Stemness Like Characteristics, and Metastasis in Human Ovarian Cancer via Activation of PI3K/Akt, β-Catenin, and Epithelial to Mesenchymal Transition Pathways
النوعArticle
رقم العدد12
رقم المجلد23
ESSN1422-0067
dc.accessType Open Access


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