Abstract
AbstractCancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, to address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed dedicated regression-based methods to analyse ribosome profiling and alternative polyadenylation data, and identified heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a translational controller of a specific mRNA regulon. We found that HNRNPC is downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3′ untranslated region lengthening and, subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. In addition, the reduced expression of HNRNPC and its regulon is associated with the worse prognosis in breast cancer patient cohorts.
Funder
United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs
U.S. Department of Health & Human Services | National Institutes of Health
European Molecular Biology Organization
Mark Foundation
Boehringer Ingelheim Fonds
RCUK | Medical Research Council
Howard Hughes Medical Institute
Mark Foundation, Atwater Foundation
American Cancer Society
Atwater Foundation
Publisher
Springer Science and Business Media LLC
Cited by
4 articles.
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