학술논문
GPCRs profiling and identification of GPR110 as a potential new target in HER2+ breast cancer.
Document Type
Academic Journal
Author
Bhat RR; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.; Yadav P; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.; Sahay D; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.; Bhargava DK; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.; Creighton CJ; Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Yazdanfard S; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.; Al-Rawi A; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA.; Yadav V; Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.; Qin L; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; Nanda S; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; Sethunath V; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; Fu X; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; De Angelis C; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; Narkar VA; Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.; Osborne CK; Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; Schiff R; Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.; Trivedi MV; Department of Pharmacy Practice and Translational Research, University of Houston, 4849 Calhoun St, Houston, TX, 77204, USA. mtrivedi@central.uh.edu.; Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. mtrivedi@central.uh.edu.; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA. mtrivedi@central.uh.edu.
Source
Publisher: Kluwer Academic Country of Publication: Netherlands NLM ID: 8111104 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7217 (Electronic) Linking ISSN: 01676806 NLM ISO Abbreviation: Breast Cancer Res Treat Subsets: MEDLINE
Subject
Language
English
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.
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.