Background: A previous report has shown that LGALS3BP (also known as 90K or Mac-2 BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin. The role of LGALS3BP in CRC prognosis was investigated. Methods: The role of LGALS3BP on CRC progression and clinical prognosis was analyzed by combining cell cultures, in vitro assays, and immunohistochemistry. Results: Silencing of LGALS3BP in HCT-116 human colon cancer cells resulted in enhanced β-catenin expression that was reversed by addition of human recombinant LGALS3BP. Moreover, intra-tumor delivery of LGALS3BP reduced tumor growth of xenografts originating from LGALS3BP-silenced HCT-116 cells. Finally, in a series of 196 CRC patients, LGALS3BP expression in tumor tissue associated with clinical outcome. Patients with high LGALS3BP expression had lower risk of relapse and a longer overall survival time than those with low LGALS3BP expression. Multivariate analyses confirmed LGALS3BP expression status as the only independent prognostic factor of survival. Conclusions: These results provide evidence that low expression of LGALS3BP participates in malignant progression of CRC and implicates poor prognosis, highlighting its augmentation as a potential therapeutic approach.

Prognostic relevance of LGALS3BP in human colorectal carcinoma

PICCOLO, Enza
;
TINARI, Nicola;ROSSI, COSMO;LA SORDA, Rossana;LATTANZIO, ROSSANO;D'EGIDIO, Maurizia;PIANTELLI, Mauro;IACOBELLI, Stefano
2015

Abstract

Background: A previous report has shown that LGALS3BP (also known as 90K or Mac-2 BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin. The role of LGALS3BP in CRC prognosis was investigated. Methods: The role of LGALS3BP on CRC progression and clinical prognosis was analyzed by combining cell cultures, in vitro assays, and immunohistochemistry. Results: Silencing of LGALS3BP in HCT-116 human colon cancer cells resulted in enhanced β-catenin expression that was reversed by addition of human recombinant LGALS3BP. Moreover, intra-tumor delivery of LGALS3BP reduced tumor growth of xenografts originating from LGALS3BP-silenced HCT-116 cells. Finally, in a series of 196 CRC patients, LGALS3BP expression in tumor tissue associated with clinical outcome. Patients with high LGALS3BP expression had lower risk of relapse and a longer overall survival time than those with low LGALS3BP expression. Multivariate analyses confirmed LGALS3BP expression status as the only independent prognostic factor of survival. Conclusions: These results provide evidence that low expression of LGALS3BP participates in malignant progression of CRC and implicates poor prognosis, highlighting its augmentation as a potential therapeutic approach.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/652908
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