Splicing Factor Ratio As an Index of Epithelial-mesenchymal Transition and Tumor Aggressiveness in Breast Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Dec 3

PMID 27911856

Citations 23

Authors

Pietro Fici

Giulia Gallerani

Anne-Pierre Morel

Laura Mercatali

Toni Ibrahim

Emanuela Scarpi

Dino Amadori

Alain Puisieux

Michel Rigaud

Francesco Fabbri

Affiliations

Soon will be listed here.

Abstract

Epithelial-to-mesenchymal transition (EMT) has been shown to be associated with tumor progression and metastasis. During this process in breast cancer, a crucial role is played by alternative splicing systems. To identify a new early prognostic marker of metastasis, we evaluated EMT-related gene expression in breast cell lines, and in primary tumor tissue from 31 patients with early breast cancer, focusing our attention on EMT-related splicing factors ESRP1, ESRP2 and RBFOX2. Results showed that the expression patterns of these genes were indicative of the onset of EMT in in-vitro models, but not in tissue samples. However, the ratio between ESRP1 or ESRP2 and RBFOX2 significantly decreased during EMT and positively correlated with the EMT-specific phenotype in cell models, representing a promising prognostic markers. Low ESRP1/RBFOX2 ratio value was associated with a higher risk of metastasis (p < 0.005) in early breast cancer patients, regardless other clinical features. A cut-off of ratio of 1.067 was determined by ROC curve analysis (AUC 0.8375; 95% CI 0.6963-0.9787). Our study show evidence that a decrease in this ratio correlates with cancer progression. The results provide a rationale for using ESRP1/RBFOX2 ratio as a new prognostic biomarker for the early prediction of metastatic potential in breast cancer.

Citing Articles

The role of ESRP1 in solid tumor development through the regulation of CD44 splicing and EMT processes.

Wang L, Zhang M, Zhao K, Yuan X, Zhao H, Liu Y Front Oncol. 2025; 15:1451130.

PMID: 40046628 PMC: 11881191. DOI: 10.3389/fonc.2025.1451130.

The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.

Herman-Sanchez N, G-Garcia M, Jimenez-Vacas J, Yubero-Serrano E, Lopez-Sanchez L, Romero-Martin S Cell Mol Life Sci. 2024; 82(1):18.

PMID: 39725737 PMC: 11671448. DOI: 10.1007/s00018-024-05515-6.

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1.

He C, Chen Y, Zhang X, Feng H, Rao Y, Ji T Sci Rep. 2024; 14(1):28475.

PMID: 39557898 PMC: 11574003. DOI: 10.1038/s41598-024-77980-9.

Alternative splicing in ovarian cancer.

Wei L, Li Y, Chen J, Wang Y, Wu J, Yang H Cell Commun Signal. 2024; 22(1):507.

PMID: 39425166 PMC: 11488268. DOI: 10.1186/s12964-024-01880-8.

RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.

Shen J, Shentu J, Zhong C, Huang Q, Duan S Clin Transl Med. 2024; 14(9):e1788.

PMID: 39243148 PMC: 11380049. DOI: 10.1002/ctm2.1788.

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