Journal
JOURNAL OF TRANSLATIONAL MEDICINE
Volume 13, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12967-015-0606-x
Keywords
LGALS3BP; beta-Catenin; Colorectal cancer; Prognosis
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Funding
- Mediapharma
- Associazione Italiana Ricerca sul Cancro (AIRC)
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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 beta-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 beta-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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