Oncotarget

Research Papers:

ERRF sensitizes ERBB2-positive breast cancer cells to lapatinib treatment likely by attenuating MCL1 and ERBB2 expression

Leilei Qi, Baotong Zhang, Shiying Zhang, Xinpei Ci, Qiao Wu, Gui Ma, Ang Luo, Liya Fu, Jamie L. King, Rita Nahta and Jin-Tang Dong _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:36054-36066. https://doi.org/10.18632/oncotarget.16425

Metrics: PDF 832 views  |   HTML 929 views  |   ?  


Abstract

Leilei Qi1, Baotong Zhang2, Shiying Zhang1, Xinpei Ci1, Qiao Wu1, Gui Ma1, Ang Luo1, Liya Fu1, Jamie L. King2, Rita Nahta3, Jin-Tang Dong1,2

1Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China

2Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, USA

3Emory Winship Cancer Institute, Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA

Correspondence to:

Jin-Tang Dong, email: j.dong@emory.edu

Keywords: ERRF, lapatinib, ERBB2, breast cancer, drug resistance

Received: December 28, 2016     Accepted: March 14, 2017     Published: March 21, 2017

ABSTRACT

Previously we found that the estrogen receptor (ER) related factor ERRF regulates cell proliferation and tumor growth, and its expression is positively associated with ER status and better survival but inversely associated with ERBB2 (also named HER2) status in breast cancer. Here we report that ERRF also plays an important role in the response of ERBB2-positive breast cancer cells to lapatinib, a dual tyrosine kinase inhibitor that interrupts the ERBB2 and EGFR pathway. In ERBB2-positive breast cancer cell lines, lower levels of ERRF expression correlated with lapatinib resistance, restoration of ERRF expression in lapatinib-resistant cell lines JIMT-1 and MDA-MB-453 enhanced their lapatinib responses, and knockdown of ERRF in lapatinib sensitive cell lines BT-474 and SK-BR-3 caused lapatinib resistance. ERRF-enhanced lapatinib sensitivity was also confirmed in xenograft tumors of JIMT-1 cells. In patients with ERBB2-positive breast cancer, higher level of ERRF expression correlated with both pathologic complete response (pCR) to lapatinib and better survival. Mechanistically, ERRF expression in resistant cells promoted lapatinib-induced apoptosis by attenuating MCL1 and ERBB2 expression. These results suggest that ERRF plays an important role in lapatinib response of ERBB2-positive breast cancer, and further study of ERRF could lead to improved prediction and sensitivity of lapatinib response.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 16425