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Resistance to radiation enhances metastasis by altering RNA metabolism

Authors: Ayush Kumar; Kensei Kishimoto; Hira L. Goel; Christi A. Silva; Rui Li; Brendan Pacheco; Lihua J. Zhu; +2 Authors

Resistance to radiation enhances metastasis by altering RNA metabolism

Abstract

The cellular programs that mediate therapy resistance are often important drivers of metastasis, a phenomenon that needs to be understood better to improve screening and treatment options for patients with cancer. Although this issue has been studied extensively for chemotherapy, less is known about a causal link between resistance to radiation therapy and metastasis. We investigated this problem in triple-negative breast cancer and established that radiation-resistant tumor cells have enhanced metastatic capacity. Resistance to radiation increases the expression of integrin β3 ( ITGB3 ), which promotes enhanced migration and invasion. Bioinformatic analysis and subsequent experimentation revealed an enrichment of RNA metabolism pathways that stabilize ITGB3 transcripts. Specifically, the RNA binding protein heterogeneous nuclear ribonucleoprotein L ( HNRNPL ), whose expression is regulated by Nrf2, mediates the formation of circular RNAs that sponge the family of let-7 microRNAs that target ITGB3 . Collectively, our findings identify a mechanism of radiation-induced metastasis that is driven by alterations in RNA metabolism.

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Keywords

NF-E2-Related Factor 2, Integrin beta3, Triple Negative Breast Neoplasms, RNA, Circular, Radiation Tolerance, Article, Gene Expression Regulation, Neoplastic, MicroRNAs, Mice, Cell Movement, Cell Line, Tumor, Humans, Animals, RNA, Female, Biomedicine and Life Sciences, Neoplasm Metastasis

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green
gold
Related to Research communities
Cancer Research