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.

Grassilli, E., Pisano, F., Cialdella, A., Bonomo, S., Missaglia, C., Cerrito, M., et al. (2016). A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation. ONCOGENE, 35(33), 4368-4378 [10.1038/onc.2015.504].

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

GRASSILLI, EMANUELA
;
BONOMO, SARA MARIA;CERRITO, MARIA GRAZIA;MASIERO, LAURA;IANZANO, LEONARDA;LEONE, BIAGIO EUGENIO;GIOVANNONI, ROBERTO;LAVITRANO, MARIALUISA
2016

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.
Articolo in rivista - Articolo scientifico
colon cancer, oncogene, Bruton's tyroine kinase, RAS
English
4368
4378
11
Grassilli, E., Pisano, F., Cialdella, A., Bonomo, S., Missaglia, C., Cerrito, M., et al. (2016). A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation. ONCOGENE, 35(33), 4368-4378 [10.1038/onc.2015.504].
Grassilli, E; Pisano, F; Cialdella, A; Bonomo, S; Missaglia, C; Cerrito, M; Masiero, L; Ianzano, L; Giordano, F; Cicirelli, V; Narloch, R; D’Amato, F; Noli, B; Ferri, G; Leone, B; Stanta, G; Bonin, S; Helin, K; Giovannoni, R; Lavitrano, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/96839
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