Panoply™ Human TMEM173 Over-expressing Stable Cell Line

Uveal melanoma (UM) is the most common intraocular malignancy in adults; currently, there are no effective treatments for metastatic UM, and patient prognosis remains poor. Stimulator of interferon genes (STING, also known as TMEM173) plays a crucial role in tumorigenesis and progression by regulating cell proliferation, metastasis, and other cellular processes. However, the specific function of STING in UM remains unclear and requires further investigation. This study analyzed STING expression to elucidate the mechanisms underlying UM development. Survival analysis revealed that high STING expression in UM tissues is associated with a poor prognosis. STING expression levels were higher in UM tissues than in choroidal tissues. Furthermore, the study found that downregulating STING expression in UM cells inhibited migration and invasion, whereas STING overexpression significantly promoted these processes; notably, STING had no significant effect on UM cell proliferation. Mechanistic studies demonstrated that STING upregulates the phosphorylation of p38 mitogen-activated protein kinase (p38-MAPK) in UM cells, thereby enhancing their migratory and invasive capabilities-an effect that could be reversed by the p38-MAPK inhibitor SB203580. In summary, this study confirms that high STING expression in UM is associated with a poor prognosis and reveals the mechanism by which STING promotes UM cell migration and invasion via the p38-MAPK signaling pathway.

To gain insight into the mechanisms by which STING induces invasion and migration in uveal melanoma (UM) cells, researchers used the Wes system to examine the expression of MAPK family members (p38-MAPK, ERK, JNK), BAP1, NF-κB (p65, p100/52), and p21. The results showed that both downregulation and upregulation of STING altered the levels of phosphorylated p38-MAPK (p-p38-MAPK) (Figure 1A), whereas the expression of ERK, JNK, BAP1, NF-κB (p65, p100/52), and p21 remained unaffected. Specifically, STING downregulation led to reduced p38-MAPK phosphorylation, while STING overexpression resulted in increased phosphorylation. Furthermore, Transwell invasion/migration assays and wound-healing assays demonstrated that treatment with the potent p38-MAPK inhibitor SB203580 (at a concentration of 10 µM) effectively reversed the STING-enhanced cell invasion and migration capabilities (Figure 1B-E). Notably, inhibition of p38-MAPK did not significantly affect UM cell proliferation, regardless of STING expression levels.

Figure 1. STING regulates the levels of p-p38-MAKP and STING-enhanced invasion and migration of UM cells can be reversed by a p38-MAPK inhibitor. (Zhou X, et al., 2024)