Article ; Online: RING finger protein TOPORS modulates the expression of tumor suppressor SMAR1 in colorectal cancer via the TLR4-TRIF pathway.
2022 Volume 16, Issue 7, Page(s) 1523–1540
Abstract: TOP1-binding arginine/serine-rich protein (TOPORS), a really interesting new gene 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 ... ...
| Abstract | TOP1-binding arginine/serine-rich protein (TOPORS), a really interesting new gene 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-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). ChIP analysis showed that TOPORS binds on the SMAR1 promoter and its occupancy increases upon LPS treatment. A previous study from our laboratory 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 toward M1 phenotype. In contrast, LPS failed to polarize tumor-associated macrophages to M1 phenotype in a SMAR1-silenced condition, which shows the involvement of SMAR1 in dictating the fate of colorectal cancer progression. Identification of the molecular mechanism behind LPS-mediated tumor regression would be crucial for designing cancer treatment strategies involving bacterial components. |
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| MeSH term(s) | Adaptor Proteins, Vesicular Transport/metabolism ; Cell Cycle Proteins/metabolism ; Colorectal Neoplasms/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism |
| Chemical Substances | Adaptor Proteins, Vesicular Transport ; Cell Cycle Proteins ; DNA-Binding Proteins ; TLR4 protein, human ; Toll-Like Receptor 4 |
| Language | English |
| Publishing date | 2022-02-05 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2415106-3 |
| ISSN | 1878-0261 ; 1574-7891 |
| ISSN (online) | 1878-0261 |
| ISSN | 1574-7891 |
| DOI | 10.1002/1878-0261.13126 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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