Breast cancer cell mesenchymal transition and metastasis directed by DAP5/eIF3d-mediated selective mRNA translation

被引：20

作者：

Alard, Amandine ^{[1
,3
]}

Katsara, Olga ^{[1
]}

Rios-Fuller, Tiffany ^{[1
]}

de la Parra, Columba ^{[1
,4
]}

Ozerdem, Ugur ^{[2
]}

Ernlund, Amanda ^{[1
,5
]}

Schneider, Robert J. ^{[1
]}

机构：

[1] NYU Sch Med, Dept Microbiol, New York, NY 10016 USA

[2] NYU Sch Med, Dept Pathol, New York, NY 10016 USA

[3] Evotech, 196 Rte Espagne, Toulouse, Occitanie, France

[4] Johns Hopkins Univ Appl Phys Lab, 11000 Johns Hopkins Rd, Laurel, MD 20723 USA

[5] CUNY Herbert H Lehman Coll, Dept Chem, Bronx, NY 10468 USA

来源：

CELL REPORTS | 2023年 / 42卷 / 06期

关键词：

CAP-INDEPENDENT TRANSLATION; THERAPEUTIC SUPPRESSION; EUKARYOTIC TRANSLATION; INITIATION; PROMOTES; EMT; PROLIFERATION; EXPRESSION; SURVIVAL; PROTEIN;

D O I：

10.1016/j.celrep.2023.112646

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cancer cell plasticity enables cell survival in harsh physiological environments and fate transitions such as the epithelial-to-mesenchymal transition (EMT) that underlies invasion and metastasis. Using genome-wide transcriptomic and translatomic studies, an alternate mechanism of cap-dependent mRNA translation by the DAP5/eIF3d complex is shown to be essential for metastasis, EMT, and tumor directed angiogenesis. DAP5/eIF3d carries out selective translation of mRNAs encoding EMT transcription factors and regulators, cell migration integrins, metalloproteinases, and cell survival and angiogenesis factors. DAP5 is overex-pressed in metastatic human breast cancers associated with poor metastasis-free survival. In human and murine breast cancer animal models, DAP5 is not required for primary tumor growth but is essential for EMT, cell migration, invasion, metastasis, angiogenesis, and resistance to anoikis. Thus, cancer cell mRNA translation involves two cap-dependent mRNA translation mechanisms, eIF4E/mTORC1 and DAP5/ eIF3d. These findings highlight a surprising level of plasticity in mRNA translation during cancer progression and metastasis.

引用

页数：21

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