title: TGFβ1-induced leucine limitation uncovered by differential ribosome codon reading.
abstract: 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 TGFβ1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine. Further analyses indicated that TGFβ1 treatment of human breast epithelial cells reduces the expression of SLC3A2, 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 TGFβ1 response, a vulnerability that might be associated with aggressiveness in cancer.
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands f.loayza@nki.nl r.agami@nki.nl.
authors.forename: Fabricio
authors.identifier: 0000-0002-2999-8594
authors.initials: F
authors.lastname: Loayza-Puch
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Koos
authors.initials: K
authors.lastname: Rooijers
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: Zijlstra
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Behzad
authors.initials: B
authors.lastname: Moumbeini
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
authors.forename: Esther A
authors.initials: EA
authors.lastname: Zaal
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Oude Vrielink
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Rui
authors.initials: R
authors.lastname: Lopes
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Ugalde
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
authors.forename: Celia R
authors.initials: CR
authors.lastname: Berkers
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands f.loayza@nki.nl r.agami@nki.nl.|Erasmus MC, Rotterdam University, Rotterdam, The Netherlands.
authors.forename: Reuven
authors.identifier: 0000-0002-2848-2473
authors.initials: R
authors.lastname: Agami
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003062:Codon; D005260:Female; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007930:Leucine / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012270:Ribosomes / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D003062:Codon; D027282:Fusion Regulatory Protein 1, Heavy Chain; C545989:SLC3A2 protein, human; D053773:Transforming Growth Factor beta1; D007930:Leucine
keywords: TGFβ; diricore; ribosome profiling