Research Paper Volume 11, Issue 24 pp 12295—12314

ERK1 indicates good prognosis and inhibits breast cancer progression by suppressing YAP1 signaling

Shiyi Yu 1, , Meng Zhang 1, , Ling Huang 1, , Zhifang Ma 1, 2, , Xue Gong 1, 2, , Weiguang Liu 1, , Jun Zhang 1, , Liming Chen 1, , Zhenghong Yu 3, , Weiyong Zhao 4, , Yan Liu 1, 5, ,

  • 1 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, P.R. China
  • 2 Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, P.R. China
  • 3 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China
  • 4 Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200336, P.R. China
  • 5 The Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, P.R. China

received: June 1, 2019 ; accepted: November 25, 2019 ; published: December 18, 2019 ;

https://doi.org/10.18632/aging.102572
How to Cite

Copyright © 2019 Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The mitogen-activated protein kinase/extracellular signal-regulated (MAPK/ERK) pathway is a well-characterized signaling pathway during the development of various cancer types. ERK1 and ERK2, the two kinase effectors of MAPK cascade, exhibit high similarity. However, it is still unknown whether these two kinases are functionally different or in contrast functionally redundant during the development of breast cancer. We found that ERK1 expression levels were significantly lower in basal breast cancer compared with luminal breast cancer and normal breast tissues. RNA sequencing data suggested that ERK1 was associated with Hippo signaling pathway and cell proliferation in breast cancer cells. The gene set enrichment analysis (GSEA) further showed enrichment for YAP1 signaling pathway in breast cancer cell lines and tumors with low expression of ERK1. Silencing of ERK1 elevated YAP1 expression and TEAD activity in breast cancer cells. Additionally, ERK1 inhibited breast cancer cell proliferation via regulation of YAP1. The Kaplan-Meier analysis of data in patients with breast cancer suggested that, higher expression of ERK1 was associated with better prognosis, whereas, higher expression of ERK2 predicted poorer prognosis. These findings unveiled the role of ERK1 on regulation of YAP1 signaling pathway, indicating ERK1 as a negative regulator of breast cancer progression.

Abbreviations

TCGA: The Cancer Genome Atlas; ERK: Extracellular regulated protein kinase; YAP1: Yes-associated protein 1; GSEA: Gene set enrichment analysis; OS: Overall Survival; DMFS: Distant metastasis free survival; GEO: Gene expression omnibus; RT-qPCR: Quantitative real-time PCR; MAPK: Mitogen-activated protein kinase; KM plotter: Kaplan-Meier Plotter; CCK-8: Cell counting kit-8; ANOVA: Analysis of variance; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; PAM50: 50-gene subtype predictor; CHX: Cycloheximide; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.