Premium
TGF β1‐induced leucine limitation uncovered by differential ribosome codon reading
Author(s) -
LoayzaPuch Fabricio,
Rooijers Koos,
Zijlstra Jelle,
Moumbeini Behzad,
Zaal Esther A,
Oude Vrielink Joachim F,
Lopes Rui,
Ugalde Alejandro P,
Berkers Celia R,
Agami Reuven
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744000
Subject(s) - leucine , amino acid , ribosome profiling , biology , amino acid transporter , cancer cell , translation (biology) , transforming growth factor , cancer research , metastasis , transporter , microbiology and biotechnology , cancer , biochemistry , messenger rna , gene , genetics
Cancer cells modulate their metabolic networks to support cell proliferation and a higher demand of building blocks. These changes may restrict the availability of certain amino acids for protein synthesis, which can be utilized for cancer therapy. However, little is known about the amino acid demand changes occurring during aggressive and invasive stages of cancer. Recently, we developed diricore, an approach based on ribosome profiling that can uncover amino acid limitations. Here, we applied diricore to a cellular model in which epithelial breast cells respond rapidly to TGF β1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine. Further analyses indicated that TGF β1 treatment of human breast epithelial cells reduces the expression of SLC 3A2, a subunit of the leucine transporter, which diminishes leucine uptake and inhibits cell proliferation. Thus, we identified a specific amino acid limitation associated with the TGF β1 response, a vulnerability that might be associated with aggressiveness in cancer.