WNT signaling pathway regulator- FRAT2 affects oncogenesis and prognosis of basal-like breast cancer

Yao Zhou; Can Li; Jie Peng; Ping Luo; Chunwei Xie; Shengshan Liu; Ge Chen; Taiyuan Li

doi:10.21037/jtd-20-1557A

WNT signaling pathway regulator- FRAT2 affects oncogenesis and prognosis of basal-like breast cancer

J Thorac Dis. 2020 Jul;12(7):3478-3487. doi: 10.21037/jtd-20-1557A.

Authors

Yao Zhou^{1

2}, Can Li³, Jie Peng⁴, Ping Luo², Chunwei Xie², Shengshan Liu², Ge Chen², Taiyuan Li⁵

Affiliations

¹ Medical College of Nanchang University, Nanchang, China.
² Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, China.
³ Queen Mary School, Medical College of Nanchang University, Nanchang, China.
⁴ School of Public Health, Nanchang University, Nanchang, China.
⁵ Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

Background: Breast cancer is the most common malignant cancer in women worldwide and is one of the leading causes of cancer death. Basal-like breast cancer (BLBC) is an aggressive subtype of breast cancer for which targeted therapy has poor efficacy. Therefore, research into the molecular pathogenesis of BLBC is urgent for developing effective targeted therapeutic treatments.

Methods: We collected relevant data from the Cancer Genome Atlas (TCGA), including transcriptome, copy number variation, and survival data. We also gathered 30 pairs clinical samples of cancer tissues and non-cancerous tissues to perform Western Blotting (WB) to reveal the encoded protein expression levels. Besides, we knocked down frequently rearranged in advanced T-cell lymphomas 2 (FRAT2) expression in two representative cell lines (T47D and MDA-MB-231 cells). The cell cycle progression was analyzed, while the apoptosis experiments were also conducted to explore the molecular pathogenesis of FRAT2 in BLBC.

Results: The aberrant activation of the WNT pathway and highly expressed FRAT2 were specifically identified across the BLBC genome comparing to other types of tumor. In addition, FRAT2 expression was found to be positively associated with its copy number variations (P=9.126×10^-23). For further investigation, we found the expression level of FRAT2 was related to the poor overall survival of BLBC patients (P=0.049). The results of WB revealed that FRTA2-encoded protein was overexpressed in BLBC tissues. Based on results in T47D and MDA-MB-231 cells in vitro, we found that knocking down FRAT2 can inhibit the proliferation of these two cell lines. In cell cycle progression experiments, cell cycle arrested in the G2/M phase. Meanwhile, increased apoptosis was also found in the shFRAT2 cell group in vitro.

Conclusions: In BLBC basal-like breast cancer, we can assume that FRAT2 is a potential treatment target.

Keywords: Basal-like breast cancer (BLBC); WNT signaling pathway; frequently rearranged in advanced T-cell lymphomas 2 (FRAT2).