التفاصيل البيبلوغرافية
| العنوان: |
Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1α. |
| المؤلفون: |
Faubert, Brandon1,2, Vincent, Emma E.1,2, Griss, Takla1,2, Samborska, Bozena1,2, Izreig, Said1,2, Svensson, Robert U.3, Mamer, Orval A.1,4, Avizonis, Daina1,4, Shackelford, David B.5, Shaw, Reuben J.3, Jones, Russell G.1,2 russell.jones@mcgill.ca |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America. 2/18/2014, Vol. 111 Issue 7, p2554-2559. 6p. |
| مصطلحات موضوعية: |
*CELLULAR control mechanisms, *KINASES, *THREONINE, *SERINE, *BIOCHEMISTRY |
| مستخلص: |
One of the major metabolic changes associated with cellular transformation is enhanced nutrient utilization, which supports tumor progression by fueling both energy production and providing bio-synthetic intermediates for growth. The liver kinase B1 (LKB1) is a serine/threonine kinase and tumor suppressor that couples bio-energetics to cell-growth control through regulation of mammalian target of rapamycin (mTOR) activity; however, the influence of LKB1 on tumor metabolism is not well defined. Here, we show that loss of LKB1 induces a progrowth metabolic program in proliferating cells. Cells lacking LKB1 display increased glucose and glutamine uptake and utilization, which support both cellular ATP levels and increased macromolecular biosynthesis. This LKB1-dependent reprogramming of cell metabolism is dependent on the hypoxia-inducible factor-1α (HIF-1α), which accumulates under normoxia in LKB1-deficient cells and is antagonized by inhibition of mTOR complex I signaling. Silencing HIF-1α reverses the metabolic advantages conferred by reduced LKB1 signaling and impairs the growth and survival of LKB1 -deficient tumor cells under low-nutrient conditions. Together, our data implicate the tumor suppressor LKB1 as a central regulator of tumor metabolism and growth control through the regulation of HIF-1α-dependent metabolic reprogramming. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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