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Accepted (AM)Open Access (License Unspecified), Open
Journal article
CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion
Cancer research (Chicago, Ill.), v 78(7), pp 1657-1671
01 Apr 2018
PMID: 29358169
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The functional significance of the chemokine receptor CCR5 in human breast cancer epithelial cells is poorly understood. Here, we report that CCR5 expression in human breast cancer correlates with poor outcome. CCR5
breast cancer epithelial cells formed mammospheres and initiated tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5-negative breast cancer cells promoted tumor metastases and induced DNA repair gene expression and activity. CCR5 antagonists Maraviroc and Vicriviroc dramatically enhanced cell killing mediated by DNA-damaging chemotherapeutic agents. Single-cell analysis revealed CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5 augments DNA repair and is reexpressed selectively on cancerous, but not normal breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific activities of DNA damage response-based treatments, allowing a dose reduction of standard chemotherapy and radiation.
This study offers a preclinical rationale to reposition CCR5 inhibitors to improve the treatment of breast cancer, based on their ability to enhance the tumor-specific activities of DNA-damaging chemotherapies administered in that disease.
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Details
- Title
- CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion
- Creators
- Xuanmao Jiao - Baruch S. Blumberg InstituteMarco A Velasco-Velázquez - Thomas Jefferson UniversityMin Wang - Baruch S. Blumberg InstituteZhiping Li - Thomas Jefferson UniversityHallgeir Rui - Medical College of WisconsinAmy R Peck - Medical College of WisconsinJames E Korkola - Oregon Health & Science UniversityXuelian Chen - University of Southern CaliforniaShaohua Xu - Thomas Jefferson UniversityJames B DuHadaway - Lankenau Institute for Medical ResearchSandra Guerrero-Rodriguez - National Autonomous University of MexicoSankar Addya - Thomas Jefferson UniversityDaniela Sicoli - Thomas Jefferson UniversityZhaomei Mu - Northwestern UniversityGang Zhang - University of Southern CaliforniaAndres Stucky - University of Southern CaliforniaXi Zhang - University of Southern CaliforniaMassimo Cristofanilli - Northwestern UniversityAlessandro Fatatis - Drexel UniversityJoe W Gray - Oregon Health & Science UniversityJiang F Zhong - University of Southern CaliforniaGeorge C Prendergast - Lankenau Institute for Medical ResearchRichard G Pestell - Nanyang Technological University
- Publication Details
- Cancer research (Chicago, Ill.), v 78(7), pp 1657-1671
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- R01 CA197903 / NCI NIH HHS R01 CA075503 / NCI NIH HHS R01 CA086072 / NCI NIH HHS R01 CA070896 / NCI NIH HHS P30 CA056036 / NCI NIH HHS R01 CA164509 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Decision Sciences (and Management Information Systems); Pharmacology and Physiology
- Web of Science ID
- WOS:000429008900007
- Scopus ID
- 2-s2.0-85047155981
- Other Identifier
- 991019167908304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology