The Circular RNA circSKA3 Binds Integrin ß1 to Induce Invadopodium Formation Enhancing Breast Cancer Invasion.
Mol Ther
; 28(5): 1287-1298, 2020 05 06.
Article
em En
| MEDLINE
| ID: mdl-32229309
ABSTRACT
Metastatic cancer cells invade surrounding tissues by forming dynamic actin-based invadopodia, which degrade the surrounding extracellular matrix and allow cancer cell invasion. Regulatory RNAs, including circular RNA, have been implicated in this process. By microarray, we found that the circular RNA circSKA3 was highly expressed in breast cancer cells and human breast cancer tissues. We further found that the invasive capacity of breast cancer cells was positively correlated with circSKA3 expression, through the formation of invadopodia. Mechanistically, we identified Tks5 and integrin ß1 as circSKA3 binding partners in these tumor-derived invadopodia. Ectopic circSKA3 expression conferred increased tumor invasiveness in vitro and in vivo. We further identified the RNA-protein binding sites between circSKA3, Tks5 and integrin ß1. In tumor formation assays, we found that circSKA3 expression promoted tumor progression and invadopodium formation. Mutation of the circSKA3 binding sites or transfection with blocking oligos abrogated the observed effects. Thus, we provide evidence that the circular RNA circSKA3 promotes tumor progression by complexing with Tks5 and integrin ß1, inducing invadopodium formation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteínas de Ciclo Celular
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Integrina beta1
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Carcinogênese
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Podossomos
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RNA Circular
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Proteínas Associadas aos Microtúbulos
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article