Panoply™ Human BSG Knockdown Stable Cell Line

Accumulating evidence indicates that solid tumors exhibit features of collective invasion, but the underlying molecular mechanisms remain unclear. Here, researchers aimed to investigate the role of CD147 (also known as BSG or EMMPRIN) in collective invasion in hepatocellular carcinoma (HCC) and its underlying mechanisms. Results indicate that human HCC exhibits collective invasion, with CD147 upregulated at the invasive front of the tumor cell cluster. Using a modified three-dimensional invasion model, researchers confirmed that CD147 promotes collective invasion, recapitulating key features of collective invasion. Transcriptome analysis and enzyme activity assays revealed that CD147 enhances the expression and activity of cathepsin B. Upregulation of cathepsin B in HCC cells promotes cell migration and invasion, thereby mediating the CD147-induced HCC invasive phenotype. Mechanistically, CD147 promotes cathepsin B transcription by activating the β-catenin signaling pathway, while reducing GSK-3β expression. Furthermore, elevated expression of CD147 and cathepsin B correlates with poor prognosis in HCC patients.

Given that CTSB transcription is regulated by β-catenin signaling, researchers investigated whether CD147 regulates β-catenin signaling in hepatocellular carcinoma (HCC). β-catenin is thought to translocate to the nucleus and activate target genes. Here, researchers found that nuclear localization of β-catenin was reduced in CD147 knockdown cells (Figure 1a-b). To confirm these results, they compared the distribution of β-catenin between the nucleus and cytoplasm. Consistent with previous results, nuclear distribution of β-catenin was significantly reduced upon CD147 knockdown (Figure 1c-d). In CD147 knockdown Huh-7 and HepG2 cells, TOP/FOP transcriptional activity was significantly attenuated (Figure 1e), indicating that CD147 knockdown attenuates β-catenin signaling. Mechanistically, CD147 knockdown enhanced the expression of GSK-3β, a component of the β-catenin destruction complex (Figure 1f-g), while CD147 overexpression had the opposite effect (Figure 1h-i). These results suggest that CD147 may activate the β-catenin signaling pathway by inhibiting the expression of GSK-3β.

Figure 1. CD147 activates β-catenin signaling via downregulating GSK-3β. (Wang S J, et al., 2020)