PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer
<p>The triple negative breast cancer (TNBC) paradox marks a major challenge in the treatment-decision making process. TNBC patients generally respond better to neoadjuvant chemotherapy compared to other breast cancer patients; however, they have a substantial higher risk of disease recurrence....
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2019
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| _version_ | 1864513566585913344 |
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| author | Ghaneya Al-Khadairi (14153274) |
| author2 | Adviti Naik (673163) Remy Thomas (702843) Boshra Al-Sulaiti (14153277) Shaheen Rizly (14153280) Julie Decock (44558) |
| author2_role | author author author author author |
| author_facet | Ghaneya Al-Khadairi (14153274) Adviti Naik (673163) Remy Thomas (702843) Boshra Al-Sulaiti (14153277) Shaheen Rizly (14153280) Julie Decock (44558) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ghaneya Al-Khadairi (14153274) Adviti Naik (673163) Remy Thomas (702843) Boshra Al-Sulaiti (14153277) Shaheen Rizly (14153280) Julie Decock (44558) |
| dc.date.none.fl_str_mv | 2019-01-03T18:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12967-018-1757-3 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/PRAME_promotes_epithelial-to-mesenchymal_transition_in_triple_negative_breast_cancer/21598443 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis PRAME PReferentially Antigen expressed in Melanoma Triple negative breast cancer Migration Invasion Epithelial-to-mesenchymal transition |
| dc.title.none.fl_str_mv | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>The triple negative breast cancer (TNBC) paradox marks a major challenge in the treatment-decision making process. TNBC patients generally respond better to neoadjuvant chemotherapy compared to other breast cancer patients; however, they have a substantial higher risk of disease recurrence. We evaluated the expression of the tumor-associated antigen PReferentially Antigen expressed in MElanoma (PRAME) as a prognostic biomarker in breast cancer and explored its role in cell migration and invasion, key hallmarks of progressive and metastatic disease. TCGA and GTeX datasets were interrogated to assess the expression of PRAME in relation to overall and disease-free survival. The role of PRAME in cell migration and invasion was investigated using gain- and loss-of-function TNBC cell line models. We show that PRAME promotes migration and invasion of TNBC cells through changes in expression of E-cadherin, N-cadherin, vimentin and ZEB1, core markers of an epithelial-to-mesenchymal transition. Mechanistic analysis of PRAME-overexpressing cells showed an upregulation of 11 genes (SNAI1, TCF4, TWIST1, FOXC2, IL1RN, MMP2, SOX10, WNT11, MMP3, PDGFRB, and JAG1) and downregulation of 2 genes (BMP7 and TSPAN13). Gene ontology analyses revealed enrichment of genes that are dysregulated in ovarian and esophageal cancer and are involved in transcription and apoptosis. In line with this, interrogation of TCGA and GTEx data demonstrated an increased PRAME expression in ovarian and esophageal tumor tissues in addition to breast tumors where it is associated with worse survival. Our findings indicate that PRAME plays a tumor-promoting role in triple negative breast cancer by increasing cancer cell motility through EMT-gene reprogramming. Therefore, PRAME could serve as a prognostic biomarker and/or therapeutic target in TNBC.</p><h2>Other Information</h2> <p> Published in: Journal of Translational Medicine<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1186/s12967-018-1757-3" target="_blank">http://dx.doi.org/10.1186/s12967-018-1757-3</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_cb8b26e7e1c12f683fff264d027265f2 |
| identifier_str_mv | 10.1186/s12967-018-1757-3 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/21598443 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancerGhaneya Al-Khadairi (14153274)Adviti Naik (673163)Remy Thomas (702843)Boshra Al-Sulaiti (14153277)Shaheen Rizly (14153280)Julie Decock (44558)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesMedical biochemistry and metabolomicsOncology and carcinogenesisPRAMEPReferentially Antigen expressed in MelanomaTriple negative breast cancerMigrationInvasionEpithelial-to-mesenchymal transition<p>The triple negative breast cancer (TNBC) paradox marks a major challenge in the treatment-decision making process. TNBC patients generally respond better to neoadjuvant chemotherapy compared to other breast cancer patients; however, they have a substantial higher risk of disease recurrence. We evaluated the expression of the tumor-associated antigen PReferentially Antigen expressed in MElanoma (PRAME) as a prognostic biomarker in breast cancer and explored its role in cell migration and invasion, key hallmarks of progressive and metastatic disease. TCGA and GTeX datasets were interrogated to assess the expression of PRAME in relation to overall and disease-free survival. The role of PRAME in cell migration and invasion was investigated using gain- and loss-of-function TNBC cell line models. We show that PRAME promotes migration and invasion of TNBC cells through changes in expression of E-cadherin, N-cadherin, vimentin and ZEB1, core markers of an epithelial-to-mesenchymal transition. Mechanistic analysis of PRAME-overexpressing cells showed an upregulation of 11 genes (SNAI1, TCF4, TWIST1, FOXC2, IL1RN, MMP2, SOX10, WNT11, MMP3, PDGFRB, and JAG1) and downregulation of 2 genes (BMP7 and TSPAN13). Gene ontology analyses revealed enrichment of genes that are dysregulated in ovarian and esophageal cancer and are involved in transcription and apoptosis. In line with this, interrogation of TCGA and GTEx data demonstrated an increased PRAME expression in ovarian and esophageal tumor tissues in addition to breast tumors where it is associated with worse survival. Our findings indicate that PRAME plays a tumor-promoting role in triple negative breast cancer by increasing cancer cell motility through EMT-gene reprogramming. Therefore, PRAME could serve as a prognostic biomarker and/or therapeutic target in TNBC.</p><h2>Other Information</h2> <p> Published in: Journal of Translational Medicine<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1186/s12967-018-1757-3" target="_blank">http://dx.doi.org/10.1186/s12967-018-1757-3</a></p>2019-01-03T18:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12967-018-1757-3https://figshare.com/articles/journal_contribution/PRAME_promotes_epithelial-to-mesenchymal_transition_in_triple_negative_breast_cancer/21598443CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215984432019-01-03T18:00:00Z |
| spellingShingle | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer Ghaneya Al-Khadairi (14153274) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis PRAME PReferentially Antigen expressed in Melanoma Triple negative breast cancer Migration Invasion Epithelial-to-mesenchymal transition |
| status_str | publishedVersion |
| title | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| title_full | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| title_fullStr | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| title_full_unstemmed | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| title_short | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| title_sort | PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Oncology and carcinogenesis PRAME PReferentially Antigen expressed in Melanoma Triple negative breast cancer Migration Invasion Epithelial-to-mesenchymal transition |