Small molecule inhibitor of Igf2bp1 represses Kras and a pro-oncogenic phenotype in cancer cells.
RNA Biol
; 19(1): 26-43, 2022.
Article
en En
| MEDLINE
| ID: mdl-34895045
ABSTRACT
Igf2bp1 is an oncofetal RNA binding protein whose expression in numerous types of cancers is associated with upregulation of key pro-oncogenic RNAs, poor prognosis, and reduced survival. Importantly, Igf2bp1 synergizes with mutations in Kras to enhance signalling and oncogenic activity, suggesting that molecules inhibiting Igf2bp1 could have therapeutic potential. Here, we isolate a small molecule that interacts with a hydrophobic surface at the boundary of Igf2bp1 KH3 and KH4 domains, and inhibits binding to Kras RNA. In cells, the compound reduces the level of Kras and other Igf2bp1 mRNA targets, lowers Kras protein, and inhibits downstream signalling, wound healing, and growth in soft agar, all in the absence of any toxicity. This work presents an avenue for improving the prognosis of Igf2bp1-expressing tumours in lung, and potentially other, cancer(s).
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas p21(ras)
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Proteínas de Unión al ARN
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Carcinogénesis
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Antineoplásicos
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article