Mouse Anti-Human LEF-1 monoclonal antibody, clone JID725

Aberrant activation of Wnt/beta-catenin pathway contributes to colorectal cancer (CRC) progression. However, little is known about regulatory mechanisms of the beta-catenin activity in cancer progression. Here we investigated the role of DBC1, which was recently reported as a negative regulator of SIRT1 and a transcriptional coactivator, in the regulation of Wnt/beta-catenin signaling. We identified the genome-wide targets of DBC1 and found that loss of DBC1 inhibits the expression of beta-catenin target genes including PROX1, a transcription factor linked to CRC progression. Mechanistically, DBC1 stabilizes LEF1-beta-catenin interaction by inhibiting SIRT1-mediated beta-catenin deacetylation, thereby enhancing LEF1-beta-catenin complex formation and long-range chromatin looping at the PROX1 locus. Furthermore, DBC1 is also required for the transcriptional activity of PROX1, suggesting that DBC1 has a dual function in regulating beta-catenin-PROX1 signaling axis: as a coactivator for both beta-catenin and PROX1. Importantly, loss of DBC1 inhibited growth and tumorigenic potential of colon cancer cells, and DBC1 expression correlated with shorter relapse-free survival in patients with advanced CRC. Our results firmly establish DBC1 as a critical positive regulator of beta-catenin-PROX1 signaling axis and a key factor in beta-catenin-PROX1-mediated CRC progression.

Objectives: ymphoid enhancer binding factor 1 (LEF1) is expressed in most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other small B-cell lymphomas. LEF1 expression has not been systematically studied in CD5-positive marginal zone lymphomas (MZLs), lymphoplasmacytic lymphomas (LPLs), and follicular lymphomas (FLs). We evaluated whether these cases lacked LEF1, helping to distinguish them from CLL/SLL. Methods: MZLs, LPLs, and FLs expressing CD5 were retrospectively studied for expression of LEF1 by immunohistochemistry. Results: LEF1 was absent in 17 of 18 CD5-positive lymphomas including 13 MZLs (2 nodal, 3 splenic, and 8 mucosa-associated lymphoid tissue lymphomas), 3 LPLs, and 1 of 2 FLs. One grade 3A CD5-positive FL expressed LEF1 in a majority of tumor cells. Conclusions: LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs.