Panoply™ Human TNFSF15 Knockdown Stable Cell Line

Metastasis is a major challenge in colorectal cancer (CRC) and a key factor contributing to its high mortality rate. Tumor necrosis factor (TNF)-like cytokine 1A (TL1A, also known as TNFSF15) is a novel regulator of inflammatory diseases. Here, researchers investigated the role of TL1A in CRC metastasis. The results demonstrated that in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model, TL1A knockdown significantly inhibited colon tumor formation, as well as the in vivo growth and pulmonary and hepatic metastasis of CRC cells. Loss of TL1A reduced the inflammatory response and inflammatory cell infiltration at tumor sites. In vitro experiments showed that TL1A knockdown suppressed CRC cell growth and metastasis and altered the expression of epithelial-mesenchymal transition (EMT)-related biomarkers. TL1A deficiency reduced TGF-β1 receptor (TβRI) levels and Smad3 phosphorylation in CRC cells. TGF-β stimulation restored the migration and invasion capabilities of CRC cells that had been suppressed by shTL1A. These findings indicate that TL1A promotes CRC tumorigenesis and metastasis and confirm that the TGF-β/Smad3 signaling pathway mediates TL1A-induced regulation of CRC cell metastasis.

In this study, researchers investigated the in vitro effects of TL1A on colorectal cancer (CRC) cells. First, compared to the normal FHC cell line, TL1A expression was observed to be significantly elevated across multiple CRC cell lines (including SW480, LoVo, SW620, RKO, and HCT116) (Figure 1A); SW480 and HCT116 cells exhibited the highest expression levels and were consequently selected for subsequent knockdown experiments. The researchers then generated TL1A-knockdown SW480 and HCT116 cell lines (Figure 1B). To explore the role of TL1A in CRC cell proliferation and metastasis, they conducted CCK-8, EdU staining, and Transwell assays. The results demonstrated that, compared to the control group, proliferation was significantly inhibited in TL1A-knockdown cells (Figure 1C and D), and the number of CRC cells undergoing migration and invasion was reduced (Figure 1E). Furthermore, TL1A knockdown led to increased E-cadherin levels and decreased Vimentin levels, further indicating that the loss of TL1A suppresses the metastatic potential of CRC cells.

Figure 1. TL1A depletion suppressed the in vitro growth and metastasis of CRC cells. (Niu W, et al., 2024)