LAUSR

TOP1-binding arginine/serine-rich protein (TOPORS), a RING finger protein, has the ability to bind to a palindromic consensus DNA sequence that enables it to function as a potential transcriptional regulator. However, its role in regulating the transcription of cancer-associated genes is yet to be explored. As toll-like receptor 4 (TLR4) agonists are known to regress solid tumors, we observed that lipopolysaccharide (LPS) induces TOPORS via a TLR4-TRIF (TIR-domain-containing adapter-inducing interferon-β)-dependent pathway, which in turn modulates the transcription of tumor suppressor scaffold/matrix attachment region-binding protein 1 (SMAR1; also known as BANP). Chromatin immunoprecipitation (ChIP) analysis showed that TOPORS binds on the SMAR1 promoter and its occupancy increases upon LPS treatment. A previous study from our lab revealed that SMAR1 acts as a repressor of signal transducer and activator of transcription 3 (STAT3) transcription. Tumor growth, as well as tumor-associated macrophage polarization, depends on the status of the STAT1:STAT3 ratio. LPS-induced SMAR1 expression decreases STAT3 expression and also skews the macrophage polarization towards M1 phenotype. In contrast, LPS failed to polarize tumor-associated macrophages (TAMs) to M1 phenotype in a SMAR1-silenced condition, which shows the involvement of SMAR1 in dictating the fate of colorectal cancer (CRC) progression. Identification of the molecular mechanism behind LPS-mediated tumor regression would be crucial for designing cancer treatment strategies involving bacterial components.