Dataset Information

MTORC2 regulates amino acid metabolism in cancer by phosphorylation of the cystine-glutamate antiporter xCT

ABSTRACT: Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N-terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic mTOR kinase inhibition, promotes glutamate secretion, cystine uptake and incorporation into glutathione linking growth factor receptor signaling with amino acid uptake and utilization. These results identify an unanticipated mechanism of amino acid metabolic reprogramming in cancer, enabling tumor cells to adapt to changing environmental conditions.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Claudio Ponte de Albuquerque

LAB HEAD: Paul S. Mischel3

PROVIDER: PXD006461 | Pride | 2017-06-28

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	XCT_SILAC2_2_HILIC10.mzXML	Mzxml
	XCT_SILAC2_2_HILIC10.pep.xml	Pepxml
	XCT_SILAC2_2_HILIC10.raw	Raw
	XCT_SILAC2_2_HILIC11.mzXML	Mzxml
	XCT_SILAC2_2_HILIC11.pep.xml	Pepxml

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Publications

mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT.

Gu Yuchao Y Albuquerque Claudio P CP Braas Daniel D Zhang Wei W Villa Genaro R GR Bi Junfeng J Ikegami Shiro S Masui Kenta K Gini Beatrice B Yang Huijun H Gahman Timothy C TC Shiau Andrew K AK Cloughesy Timothy F TF Christofk Heather R HR Zhou Huilin H Guan Kun-Liang KL Mischel Paul S PS

Molecular cell 20170622 1

Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) ...[more]

PMID: 28648777

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