mTOR links oncogenic signaling to tumor cell metabolism
- PMID: 21301797
- DOI: 10.1007/s00109-011-0726-6
mTOR links oncogenic signaling to tumor cell metabolism
Abstract
As a key regulator of cell growth and proliferation, the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) has been the subject of intense investigation for its role in tumor development and progression. This research has revealed a signaling network of oncogenes and tumor suppressors lying upstream of mTORC1, and oncogenic perturbations to this network result in the aberrant activation of this kinase complex in the majority of human cancers. However, the molecular events downstream of mTORC1 contributing to tumor cell growth and proliferation are just coming to light. In addition to its better-known functions in promoting protein synthesis and suppressing autophagy, mTORC1 has emerged as a key regulator of cellular metabolism. Recent studies have found that mTORC1 activation is sufficient to stimulate an increase in glucose uptake, glycolysis, and de novo lipid biosynthesis, which are considered metabolic hallmarks of cancer, as well as the pentose phosphate pathway. Here, we focus on the molecular mechanisms of metabolic regulation by mTORC1 and the potential consequences for anabolic tumor growth and therapeutic strategies.
Similar articles
-
Transcriptional control of cellular metabolism by mTOR signaling.Cancer Res. 2011 Apr 15;71(8):2815-20. doi: 10.1158/0008-5472.CAN-10-4158. Epub 2011 Apr 12. Cancer Res. 2011. PMID: 21487041 Free PMC article.
-
A growing role for mTOR in promoting anabolic metabolism.Biochem Soc Trans. 2013 Aug;41(4):906-12. doi: 10.1042/BST20130041. Biochem Soc Trans. 2013. PMID: 23863154 Review.
-
Activation of a metabolic gene regulatory network downstream of mTOR complex 1.Mol Cell. 2010 Jul 30;39(2):171-83. doi: 10.1016/j.molcel.2010.06.022. Mol Cell. 2010. PMID: 20670887 Free PMC article.
-
Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells.PLoS One. 2015 Jul 15;10(7):e0132880. doi: 10.1371/journal.pone.0132880. eCollection 2015. PLoS One. 2015. PMID: 26176608 Free PMC article.
-
The expanding role of mTOR in cancer cell growth and proliferation.Mutagenesis. 2015 Mar;30(2):169-76. doi: 10.1093/mutage/geu045. Mutagenesis. 2015. PMID: 25688110 Free PMC article. Review.
Cited by
-
Signal integration by mTORC1 coordinates nutrient input with biosynthetic output.Nat Cell Biol. 2013 Jun;15(6):555-64. doi: 10.1038/ncb2763. Nat Cell Biol. 2013. PMID: 23728461 Free PMC article. Review.
-
Intersections between mitochondrial sirtuin signaling and tumor cell metabolism.Crit Rev Biochem Mol Biol. 2015;50(3):242-55. doi: 10.3109/10409238.2015.1031879. Epub 2015 Apr 21. Crit Rev Biochem Mol Biol. 2015. PMID: 25898275 Free PMC article. Review.
-
mTOR-Dependent Role of Sestrin2 in Regulating Tumor Progression of Human Endometrial Cancer.Cancers (Basel). 2020 Sep 4;12(9):2515. doi: 10.3390/cancers12092515. Cancers (Basel). 2020. PMID: 32899752 Free PMC article.
-
Elevated protein kinase D3 (PKD3) expression supports proliferation of triple-negative breast cancer cells and contributes to mTORC1-S6K1 pathway activation.J Biol Chem. 2014 Feb 7;289(6):3138-47. doi: 10.1074/jbc.M113.502633. Epub 2013 Dec 11. J Biol Chem. 2014. PMID: 24337579 Free PMC article.
-
mTORC1-driven accumulation of the oncometabolite fumarate as a potential critical step in renal cancer progression.Mol Cell Oncol. 2018 Nov 20;6(1):1537709. doi: 10.1080/23723556.2018.1537709. eCollection 2019. Mol Cell Oncol. 2018. PMID: 30788416 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous