A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation

D'AMATO, FILOMENA;NOLI, BARBARA;FERRI, GIAN LUCA;
2016-01-01

Abstract

Bruton’s tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5’-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach
2016
2016
Inglese
35
33
4368
4378
11
http://www.nature.com/onc/index.html
Esperti anonimi
internazionale
scientifica
molecular biology; cancer research; genetics
Grassilli, E; Pisano, F; Cialdella, A; Bonomo, S; Missaglia, C; Cerrito, Mg; Masiero, L; Ianzano, L; Giordano, F; Cicirelli, V; Narloch, R; D'Amato, F ...espandi
1.1 Articolo in rivista
info:eu-repo/semantics/article
1 Contributo su Rivista::1.1 Articolo in rivista
262
20
open
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