Tumor suppressive function of Matrin 3 in the basal-like breast cancer

Jaehyuk Yang,Yongseok Kwon,Li Ma,Jongchan Kim,Seung Jun Lee

doi:10.1186/s40659-020-00310-6

Abstract

BackgroundBasal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized.MethodsWe analyzed in vitro tumorigenecity by cell proliferation and soft agar colony formation assays, apoptotic cell death by flow cytometry and Poly (ADP-ribose) polymerase (PARP) cleavage, epithelial-mesenchymal transition (EMT) by checking specific EMT markers with real-time quantitative PCR and in vitro migration and invasion by Boyden Chamber assays. To elucidate the underlying mechanism by which MATR3 functions as a tumor suppressor, we performed Tandem affinity purification followed by mass spectrometry (TAP-MS) and pathway analysis. We also scrutinized MATR3 expression levels in the different subtypes of human breast cancer and the correlation between MATR3 expression and patient survival by bioinformatic analyses of publicly available transcriptome datasets.ResultsMATR3 suppressed in vitro tumorigenecity, promoted apoptotic cell death and inhibited EMT, migration, and invasion in BLBC/TNBC cells. Various proteins regulating apoptosis were identified as MATR3-binding proteins, and YAP/TAZ pathway was suppressed by MATR3. MATR3 expression was inversely correlated with the aggressive and metastatic nature of breast cancer. Moreover, high expression levels of MATR3 were associated with a good prognosis of breast cancer patients.ConclusionsOur data demonstrate that MATR3 functions as a putative tumor suppressor in BLBC/TNBC cells. Also, MATR3 potentially plays a role as a biomarker in predicting chemotherapy-sensitivity and patient survival in breast cancer patients.

Highlights

Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer
We examined whether Matrin 3 (MATR3) levels influence the basal cell proliferation, and found that MATR3 overexpression inhibited and its depletion increased in vitro cell proliferation in MDA-MB-231 and BT549 cells, respectively (Fig. 1d)
By analyzing breast cancer patient survivals with Kaplan–Meier plots, we found that high expression levels of MATR3 are associated with better patient relapse-free survival (RFS) (Fig. 7a), overall survival (OS) (Fig. 7b) and metastatic relapsefree survival (MRFS) (Fig. 7c), which strongly suggests that high MATR3 expression in breast cancer could potentially be a prognostic biomarker to predict better breast cancer patient survival

Summary

Introduction

Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized. Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is characterized by a lack of hormone receptors (estrogen receptor and progesterone receptor) and high expression or amplification of human epidermal growth factor receptor 2 (HER2) [1, 2]. CTNNA1, encoding α-catenin, has been shown to have tumor-suppressive functions in E-cadherin-negative BLBC [12], which suggests that MATR3 may function as a tumor suppressor gene but its role in cancer remains elusive

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