Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin

被引：40

作者：

Flores, A. ^{[1
,2
,7
]}

Sandoyal-Gonzalez, S. ^{[1
]}

Takahashi, R. ^{[3
]}

Krall, A. ^{[4
]}

Sathe, L. ^{[1
]}

Wei, L. ^{[5
]}

Radu, C. ^{[5
]}

Jolly, J. ^{[6
]}

Graham, N. ^{[6
]}

Christofk, H. R. ^{[4
,5
,7
,8
]}

Lowry, W. E. ^{[1
,2
,3
,7
,8
]}

机构：

[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Broad Ctr Regenerat Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Pharmacol, Los Angeles, CA 90095 USA

[6] USC, Dept Engn, Los Angeles, CA 90089 USA

[7] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

GLUTAMINASE ACTIVITY; SELF-RENEWAL; CANCER; METABOLISM; INHIBITION; GLYCOLYSIS; MARKER; LGR5;

D O I：

10.1038/s41467-018-07857-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.

引用

页数：14

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