ArticleCurrent biology : CB2016
The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis.
Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 69 citations in OpenAlex.
- Quantitative and qualitative metrics of tumor stroma in predicting ovarian cancer outcomes and expansion of its study with AI-based tools.Molecular therapy. Oncology · 2025Review
- Pan-cancer analysis identifies tRNA modification enzyme CTU2 as a novel tumor biomarker and its role in immune microenvironment.Frontiers in immunology · 2025Article
- Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.Cancer metastasis reviews · 2024Review
- COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer.International journal of molecular sciences · 2024Article
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- Selection of tRNA Genes in Human Breast Tumours Varies Substantially between Individuals.Cancers · 2023Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- The In Vitro Effects of Romina Strawberry Extract on 3D Uterine Leiomyosarcoma Cells.Nutrients · 2023Article
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- Inhibition of lncRNA RPPH1 activity decreases tumor proliferation and metastasis through down-regulation of inflammation-related oncogenes.American journal of translational research · 2023Article
- tRNA dysregulation and disease.Nature reviews. Genetics · 2022Review
- The Aminoacyl-tRNA Synthetase and tRNA Expression Levels Are Deregulated in Cancer and Correlate Independently with Patient Survival.Current issues in molecular biology · 2022Article
- Widespread association of ERα with RMRP and tRNA genes in MCF-7 cells and breast cancers.Gene · 2022Article
- Protein synthesis control in cancer: selectivity and therapeutic targeting.The EMBO journal · 2022Review
- Transfer RNAs-derived small RNAs and their application potential in multiple diseases.Frontiers in cell and developmental biology · 2022Review
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- Codon optimality in cancer.Oncogene · 2021Review
- Metabolic dysfunction and inflammatory disease: the role of stromal fibroblasts.The FEBS journal · 2021Review
- The plasticity of mRNA translation during cancer progression and therapy resistance.Nature reviews. Cancer · 2021Review
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25 authors at 6 institutions in 2 countries.
Funding
Abstract
Expression of the initiator methionine tRNA (tRNAi(Met)) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi(Met) expression levels influence tumor progression. We have found that tRNAi(Met) expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi(Met) in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi(Met) contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi(Met) gene (2+tRNAi(Met) mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi(Met) mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi(Met) mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi(Met) significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi(Met)-overexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi(Met)-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi(Met) mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi(Met) levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis.
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