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
<p dir="ltr">Ovarian 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 a...
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| مؤلفون آخرون: | , , , , |
| منشور في: |
2022
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| _version_ | 1864513548252610560 |
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| author | Lubna Therachiyil (4246156) |
| author2 | Roopesh Krishnankutty (1297770) Fareed Ahmad (134672) Jericha M. Mateo (17563293) Shahab Uddin (154400) Hesham M. Korashy (1474849) |
| author2_role | author author author author author |
| author_facet | Lubna Therachiyil (4246156) Roopesh Krishnankutty (1297770) Fareed Ahmad (134672) Jericha M. Mateo (17563293) Shahab Uddin (154400) Hesham M. Korashy (1474849) |
| author_role | author |
| dc.creator.none.fl_str_mv | Lubna Therachiyil (4246156) Roopesh Krishnankutty (1297770) Fareed Ahmad (134672) Jericha M. Mateo (17563293) Shahab Uddin (154400) Hesham M. Korashy (1474849) |
| dc.date.none.fl_str_mv | 2022-06-07T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ijms23126395 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Aryl_Hydrocarbon_Receptor_Promotes_Cell_Growth_Stemness_Like_Characteristics_and_Metastasis_in_Human_Ovarian_Cancer_via_Activation_of_PI3K_Akt_-Catenin_and_Epithelial_to_Mesenchymal_Transition_Pathways/29069588 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences ovarian cancer aryl hydrocarbon receptor chemoresistance EMT apoptosis stemness |
| dc.title.none.fl_str_mv | 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 |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Ovarian 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.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms23126395" target="_blank">https://dx.doi.org/10.3390/ijms23126395</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_2615d25ce3b023120c1d5dc471efb682 |
| identifier_str_mv | 10.3390/ijms23126395 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29069588 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | 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 PathwaysLubna Therachiyil (4246156)Roopesh Krishnankutty (1297770)Fareed Ahmad (134672)Jericha M. Mateo (17563293)Shahab Uddin (154400)Hesham M. Korashy (1474849)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisPharmacology and pharmaceutical sciencesovarian canceraryl hydrocarbon receptorchemoresistanceEMTapoptosisstemness<p dir="ltr">Ovarian 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.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms23126395" target="_blank">https://dx.doi.org/10.3390/ijms23126395</a></p>2022-06-07T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms23126395https://figshare.com/articles/journal_contribution/Aryl_Hydrocarbon_Receptor_Promotes_Cell_Growth_Stemness_Like_Characteristics_and_Metastasis_in_Human_Ovarian_Cancer_via_Activation_of_PI3K_Akt_-Catenin_and_Epithelial_to_Mesenchymal_Transition_Pathways/29069588CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/290695882022-06-07T03:00:00Z |
| spellingShingle | 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 Lubna Therachiyil (4246156) Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences ovarian cancer aryl hydrocarbon receptor chemoresistance EMT apoptosis stemness |
| status_str | publishedVersion |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences ovarian cancer aryl hydrocarbon receptor chemoresistance EMT apoptosis stemness |