Abstract
BackgroundA 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.MethodsThe role of LGALS3BP on CRC progression and clinical prognosis was analyzed by combining cell cultures, in vitro assays, and immunohistochemistry.ResultsSilencing 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.ConclusionsThese 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.
Highlights
A previous report has shown that LGALS3BP has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin
LGALS3BP‐silenced CRC cells grow larger tumors, an effect which is reversed by intratumor injection of LGALS£BP To investigate the role of LGALS3BP on tumor growth, short hairpin RNA constructs were generated to stably knock-down LGALS3BP in HCT-116 cells (HCT116shLGALS3BP)
Expression of LGALS3BP protein was assessed by Western blotting (Fig. 1 box) and Enzyme‐linked immunosorbent assay (ELISA) assay on the conditioned medium of both cell lines (185.5 ng/mL in HCT-116shctrl vs. 40.1 ng/mL in HCT116shLGALS3BP cells)
Summary
A previous report has shown that LGALS3BP ( 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. There is a considerable risk of recurrence in patients with stage II and III disease. Recurrence occurs in ~20% of stage II patients and ~50% of the stage III patients may be cured with surgery alone [1,2,3]. It is critical to identify patients with a high risk of recurrence. LGALS3BP is a large oligomeric, highly glycosylated protein composed of ≈90 kDa subunits that was originally identified as a tumor-secreted antigen [4] and as a ligand of the lactose-specific S-type lectin, galectin-3 (formerly Mac-2) [5].
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