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;Giordano, F;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
25-gen-2016
2016
35
33
4368
4378
partially_open
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].
File in questo prodotto:
File Dimensione Formato  
oncogene2016.pdf

accesso aperto

Descrizione: articolo + materiali supplementari
Tipologia di allegato: Author’s Accepted Manuscript, AAM (Post-print)
Dimensione 6.02 MB
Formato Adobe PDF
6.02 MB Adobe PDF Visualizza/Apri
A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation - onc2015504a.pdf

Solo gestori archivio

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 3.7 MB
Formato Adobe PDF
3.7 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/96839
Citazioni
  • Scopus 52
  • ???jsp.display-item.citation.isi??? 50
Social impact