Gpr132 sensing of lactate mediates tumor–macrophage interplay to promote breast cancer metastasis
Abstract
Metastasis is a major cause of cancer mortality. However, the regulation of this complex process remains poorly understood. Due to low oxygen supply and enhanced sugar metabolism, cancer cells releases lactate to create an acidic environment. We show that a membrane receptor on macrophages called G protein-coupled receptor 132 (Gpr132) can sense and respond to this lactate signal from cancer cells. As a result, macrophages alter their functions, which, in turn, stimulates cancer metastasis to distant organs. Consequently, loss of Gpr132 in mice inhibits breast cancer metastasis; lower Gpr132 expression in patients with breast cancer correlates with better metastasis-free survival. These findings uncover knowledge and potentially novel treatment for cancer metastasis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 03, 2017
- Source ID
- 10.1073/pnas.1614035114
Entities
People
- Alan Saghatelian
- Daniel J Siegwart
- Hao Zuo
- Hu Xiong
- Matthew J. Kolar
- Peiwen Chen
- Qian Chu
- Yihong Wan
Organizations
- Cancer Prevention and Research Institute of Texas
- Mary Kay Foundation
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Robert A. Welch Foundation
- Salk Institute for Biological Studies
- United States Department of Defense
- University of Texas at Austin