Panoply™ Human TMEM173 Knockdown Stable Cell Line

The relationship between human epidermal growth factor receptor 2 (HER2), the cGAS-STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway, and autophagy in gastric cancer remains unclear. In this study, researchers investigated whether HER2 regulates autophagy in gastric cancer cells via the cGAS-STING signaling pathway, thereby influencing key processes such as cell proliferation and migration. Using techniques including lentiviral transfection, CCK-8 assays, colony formation assays, Transwell migration assays, wound healing assays, and siRNA-mediated knockdown, the researchers found that HER2 overexpression inhibited the cGAS-STING pathway and autophagy while enhancing the migratory capacity of gastric cancer cells; conversely, HER2 knockdown activated the cGAS-STING pathway, promoted autophagy, and reduced migratory capacity. They further observed that inhibiting autophagy with chloroquine (CQ) enhanced the migration of HER2-overexpressing cells. Moreover, silencing STING expression reversed the migration defects caused by HER2 knockdown, highlighting the pivotal role of the cGAS-STING pathway in HER2-mediated regulation of cell migration. The study also revealed that high STING (also known as TMEM173) expression in gastric cancer was significantly associated with poor prognosis, and STING expression was identified as an independent prognostic factor for survival. These findings underscore the importance of HER2-mediated regulation of autophagy via the cGAS-STING pathway in gastric cancer progression and highlight the potential of this pathway as a therapeutic target.

To investigate the link between HER2 and the cGAS-STING pathway, researchers generated STING-knockdown MGC803 cells. Western blot (WB) analysis confirmed that in the STING-knockdown cell line, STING expression was reduced, P62 levels were elevated, and LC3B/A levels were decreased (Figure 1c), indicating that STING knockdown inhibited autophagy. Transwell assays (Figure 1a) and wound-healing assays (Figure 1b) demonstrated that STING knockdown significantly enhanced cell migration. These results suggest that reduced STING expression promotes gastric cancer cell migration. The researchers subsequently performed rescue experiments by knocking down STING in HER2-knockdown cells. The results showed that HER2 knockdown led to increased STING levels and enhanced autophagy (evidenced by decreased P62 and increased LC3 conversion; Figure 1d), whereas STING knockdown reversed these effects, confirming that HER2 inhibits autophagy by suppressing the cGAS-STING pathway. The rescue experiments further demonstrated that while HER2 knockdown inhibited cell migration, subsequent STING knockdown restored migratory capacity (Figure 1e and f). These findings suggest that HER2 inhibits autophagy via the cGAS-STING pathway, thereby promoting cell migration.

Figure 1. HER2 promotes migration by suppressing autophagy via the cGAS-STING pathway. (Liang P, et al., 2025)