Article open access publication

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

Oncogene, Springer Nature, ISSN 0950-9232

Volume 35, 33, 2016

DOI:10.1038/onc.2015.504, Dimensions: pub.1043263135, PMC: PMC4994017, PMID: 26804170,

Authors

Grassilli, E * (1) (2)
Pisano, F (1) (2)
Cialdella, A (1) (2)
Bonomo, S (2)
Noli, B (3)
Stanta, G (4)
Bonin, S (4)
Helin, K (5)
Lavitrano, M * (2)

* Corresponding author

Affiliations

Organisations

  1. (1) BiOnSil srl, Monza, Italy
  2. (2) University of Milano-Bicocca, grid.7563.7
  3. (3) University of Cagliari, grid.7763.5
  4. (4) Department of Medical Sciences, University of Trieste, Cattinara Hospital, Trieste, Italy
  5. (5) University of Copenhagen, grid.5254.6, KU

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Italy

Denmark

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Europe

Description

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.

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Times Cited: 23

Field Citation Ratio (FCR): 7.69

Relative Citation ratio (RCR): 1.33

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