PRAME Promotes Epithelial-to-mesenchymal Transition in Triple Negative Breast Cancer

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2019 Jan 4

PMID 30602372

Citations 25

Authors

Ghaneya Al-Khadairi

Adviti Naik

Remy Thomas

Boshra Al-Sulaiti

Shaheen Rizly

Julie Decock

Affiliations

Soon will be listed here.

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.

Citing Articles

The Utilization of PRAME in the Diagnosis, Prognosis, and Treatment of Melanoma.

Blount S, Liu X, McBride J Cells. 2024; 13(20.

PMID: 39451258 PMC: 11505691. DOI: 10.3390/cells13201740.

The LDHC-STAT3 Signaling Network Is a Key Regulator of Basal-like Breast Cancer Cell Survival.

Naik A, Thomas R, Sikhondze M, Babiker A, Lattab B, Qasem H Cancers (Basel). 2024; 16(13).

PMID: 39001513 PMC: 11240808. DOI: 10.3390/cancers16132451.

Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes.

Kaczorowski M, Lasota J, Dudek K, Malkiewicz B, Miettinen M, Halon A J Clin Med. 2024; 13(6).

PMID: 38541782 PMC: 10971184. DOI: 10.3390/jcm13061554.

PRAME Expression: A Target for Cancer Immunotherapy and a Prognostic Factor in Uveal Melanoma.

Gelmi M, Gezgin G, van der Velden P, Luyten G, Luk S, Heemskerk M Invest Ophthalmol Vis Sci. 2023; 64(15):36.

PMID: 38149971 PMC: 10755595. DOI: 10.1167/iovs.64.15.36.

PRAME induces genomic instability in uveal melanoma.

Kurtenbach S, Sanchez M, Kuznetsoff J, Rodriguez D, Weich N, Dollar J Oncogene. 2023; 43(8):555-565.

PMID: 38030788 PMC: 10873199. DOI: 10.1038/s41388-023-02887-0.

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