PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

Ghaneya Al-Khadairi, Adviti Naik, Remy Thomas, Boshra Al-Sulaiti, Shaheen Rizly, Julie Decock

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number9
JournalJournal of Translational Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - 3 Jan 2019

Fingerprint

Triple Negative Breast Neoplasms
Epithelial-Mesenchymal Transition
Oncology
Melanoma
Carcinogenesis
Health
Antigens
Genes
Tumors
Cell Movement
Cadherins
Breast Neoplasms
Biomarkers
Platelet-Derived Growth Factor beta Receptor
Cells
Neoplasms
Gene Ontology
Neoplasm Antigens
Vimentin
Chemotherapy

Keywords

  • Epithelial-to-mesenchymal transition
  • Invasion
  • Migration
  • PRAME
  • PReferentially Antigen expressed in Melanoma
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis. / Al-Khadairi, Ghaneya; Naik, Adviti; Thomas, Remy; Al-Sulaiti, Boshra; Rizly, Shaheen; Decock, Julie.

In: Journal of Translational Medicine, Vol. 17, No. 1, 9, 03.01.2019.

Research output: Contribution to journalArticle

@article{e45b6e2a26e94d3d93656eb5730a1fd3,
title = "PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis",
abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "Epithelial-to-mesenchymal transition, Invasion, Migration, PRAME, PReferentially Antigen expressed in Melanoma, Triple negative breast cancer",
author = "Ghaneya Al-Khadairi and Adviti Naik and Remy Thomas and Boshra Al-Sulaiti and Shaheen Rizly and Julie Decock",
year = "2019",
month = "1",
day = "3",
doi = "10.1186/s12967-018-1757-3",
language = "English",
volume = "17",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

AU - Al-Khadairi, Ghaneya

AU - Naik, Adviti

AU - Thomas, Remy

AU - Al-Sulaiti, Boshra

AU - Rizly, Shaheen

AU - Decock, Julie

PY - 2019/1/3

Y1 - 2019/1/3

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - Epithelial-to-mesenchymal transition

KW - Invasion

KW - Migration

KW - PRAME

KW - PReferentially Antigen expressed in Melanoma

KW - Triple negative breast cancer

UR - http://www.scopus.com/inward/record.url?scp=85059380546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059380546&partnerID=8YFLogxK

U2 - 10.1186/s12967-018-1757-3

DO - 10.1186/s12967-018-1757-3

M3 - Article

VL - 17

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 9

ER -