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Breast Cancer Res Treat. 2018 Jul;170(2):279-292. doi: 10.1007/s10549-018-4751-9. Epub 2018 Mar 24.

GPCRs profiling and identification of GPR110 as a potential new target in HER2+ breast cancer.

Author information

1
Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.
2
Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
3
Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
4
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
5
Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA. mtrivedi@central.uh.edu.
6
Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. mtrivedi@central.uh.edu.
7
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA. mtrivedi@central.uh.edu.

Abstract

PURPOSE:

G protein-coupled receptors (GPCRs) represent the largest family of druggable targets in human genome. Although several GPCRs can cross-talk with the human epidermal growth factor receptors (HERs), the expression and function of most GPCRs remain unknown in HER2+ breast cancer (BC). In this study, we aimed to evaluate gene expression of GPCRs in tumorigenic or anti-HER2 drug-resistant cells and to understand the potential role of candidate GPCRs in HER2+ BC.

METHODS:

Gene expression of 352 GPCRs was profiled in Aldeflur+ tumorigenic versus Aldeflur- population and anti-HER2 therapy-resistant derivatives versus parental cells of HER2+ BT474 cells. The GPCR candidates were confirmed in 7 additional HER2+ BC cell line models and publicly available patient dataset. Anchorage-dependent and anchorage-independent cell growth, mammosphere formation, and migration/invasion were evaluated upon GPR110 knockdown by siRNA in BT474 and SKBR3 parental and lapatinib+ trastuzumab-resistant (LTR) cells.

RESULTS:

Adhesion and class A GPCRs were overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population of BT474 cells, respectively. GPR110 was the only GPCR overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population in BT474, SKBR3, HCC1569, MDA-MB-361, AU565, and/or HCC202 cells and in HER2+ BC subtype in patient tumors. Using BT474 and SKBR3 parental and LTR cells, we found that GPR110 knockdown significantly reduced anchorage-dependent/independent cell growth as well as migration/invasion of parental and LTR cells and mammosphere formation in LTR derivatives and not in parental cells.

CONCLUSION:

Our data suggest a potential role of GPR110 in tumorigenicity and in tumor cell dissemination in HER2+ BC.

KEYWORDS:

Breast cancer; Drug resistance; Drug targets; GPR110; HER2; Tumorigenesis

PMID:
29574636
PMCID:
PMC6110614
[Available on 2019-07-01]
DOI:
10.1007/s10549-018-4751-9
[Indexed for MEDLINE]

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