Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel

Ying Jin; Wenquan Hu; Tong Liu; Ujala Rana; Irene Aguilera-Barrantes; Amanda Kong; Suresh N Kumar; Bei Wang; Pin Gao; Xiang Wang; Yajun Duan; Aiping Shi; Dong Song; Ming Yang; Sijie Li; Bing Han; Gang Zhao; Zhimin Fan; Qing Robert Miao

doi:10.1016/j.canlet.2018.01.054

Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel

Cancer Lett. 2018 Apr 10:419:233-244. doi: 10.1016/j.canlet.2018.01.054. Epub 2018 Feb 2.

Authors

Ying Jin¹, Wenquan Hu², Tong Liu³, Ujala Rana², Irene Aguilera-Barrantes⁴, Amanda Kong⁵, Suresh N Kumar⁶, Bei Wang⁷, Pin Gao¹, Xiang Wang², Yajun Duan⁸, Aiping Shi⁹, Dong Song⁹, Ming Yang⁹, Sijie Li⁹, Bing Han⁹, Gang Zhao⁹, Zhimin Fan¹⁰, Qing Robert Miao¹¹

Affiliations

¹ Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China; Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA.
² Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA.
³ Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin, 130033, China.
⁴ Department of Pathology, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA.
⁵ Department of Surgery, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA.
⁶ Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA.
⁷ Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
⁸ Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
⁹ Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
¹⁰ Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. Electronic address: fanzhimn@163.com.
¹¹ Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA; Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA. Electronic address: qmiao@mcw.edu.

Abstract

Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor α (ERα) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a potential therapeutic target for ERα positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ERα positive breast cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR knockdown attenuated either 17β-estradiol or epidermal growth factor stimulated phosphorylation of ERα at Serine 118 residue. The ChIP-PCR assay further demonstrated that NgBR knockdown decreased ERα binding to the estrogen response element (ERE) of the ERα target gene and increased the binding of p53 to the promoter region of survivin to attenuate survivin transcription. In summary, our data suggest that NgBR expression is essential to promoting ERα positive breast cancer cell resistance to paclitaxel. Findings from this study implicate a novel therapeutic target for treating ERα positive breast cancer in neo-adjuvant/adjuvant chemotherapy.

Keywords: Breast cancer; Estrogen receptor; Nogo-B receptor; Paclitaxel; Survivin; p53.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / therapeutic use
Apoptosis / drug effects
Apoptosis / genetics
Breast Neoplasms / drug therapy*
Breast Neoplasms / genetics
Breast Neoplasms / metabolism
Cell Line, Tumor
Drug Resistance, Neoplasm / drug effects*
Drug Resistance, Neoplasm / genetics
Estradiol / pharmacology
Estrogens / pharmacology
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
MCF-7 Cells
Paclitaxel / therapeutic use*
Phosphorylation / drug effects
RNA Interference
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Receptors, Estrogen / metabolism*

Substances

Antineoplastic Agents, Phytogenic
Estrogens
NUS1 protein, human
Receptors, Cell Surface
Receptors, Estrogen
Estradiol
Paclitaxel

Grants and funding

R01 HL108938/HL/NHLBI NIH HHS/United States