Oncogenic PI3K promotes methionine dependency in breast cancer cells through the cystine-glutamate antiporter xCT.

ABSTRACT: The precursor homocysteine is metabolized either through the methionine cycle to produce methionine or through the transsulfuration pathway to synthesize cysteine. Alternatively, cysteine can be obtained through uptake of its oxidized form, cystine. Many cancer cells exhibit methionine dependency such that their proliferation is impaired in growth media in which methionine is replaced by homocysteine. We showed that oncogenic PIK3CA and decreased expression of SLC7A11, a gene that encodes a cystine transporter also known as xCT, correlated with increased methionine dependency in breast cancer cells. Oncogenic PIK3CA was sufficient to confer methionine dependency to mammary epithelial cells, partly by decreasing cystine uptake through the transcriptional and posttranslational inhibition of

SUBMITTER: Lien EC 

PROVIDER: S-EPMC5808948 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature