Journal
CELL REPORTS
Volume 14, Issue 7, Pages 1590-1601Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.01.057
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Funding
- UCLA Scholars in Oncologic Molecular Imaging (SOMI) program
- NIH [R25T CA098010]
- Early Detection Research Network [NCI CA86366, NCI CA152751]
- NIH NCATS
- UCLA CTSI [UL1TR000124]
- National Cancer Institute/NIH [P01 CA168585]
- American Cancer Society Research Scholar Award [RSG-12-257-01-TBE]
- Melanoma Research Alliance Established Investigator Award [20120279]
- UCLA Jonsson Cancer Center Foundation
- Damon Runyon Cancer Research Foundation
- Searle Scholars Program
- NIH Director's New Innovator Award [DP2 OD008454-01]
- Caltech/UCLA Nanosystems Biology Cancer Center [NCI U54 CA151819]
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Monocarboxylate transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here, we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export that when inhibited, enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors, further supporting their use as anti-cancer therapeutics.
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