Solute carrier family 34, member 2 (SLC34A2) has been implicated in the development and progression of various malignancies. However, the clinical significance of SLC34A2 in esophageal squamous cell carcinoma (ESCC) and its underlying molecular mechanisms remain unclear. Here, researchers demonstrate that SLC34A2 expression is significantly upregulated in ESCC and correlates with adverse clinicopathological features (particularly Ki-67 labeling index) and poor prognosis in ESCC patients. Overexpression of SLC34A2 promotes ESCC cell proliferation, while silencing of SLC34A2 has the opposite effect. Furthermore, SLC34A2 induces autophagy, promoting ESCC cell proliferation, whereas inhibition of autophagy inhibits it. Further studies revealed that SLC34A2 interacts with the autophagy-related protein STX17, promoting autophagy and proliferation in ESCC cells by inhibiting STX17 ubiquitination and degradation. These findings suggest that SLC34A2 may serve as a prognostic biomarker for ESCC.
Based on the close relationship between high SLC34A2 expression and elevated Ki-67 labeling, the researchers investigated the effect of SLC34A2 on ESCC cell proliferation. First, they generated SLC34A2-overexpressing KYSE520 and KYSE140 cells (Figure 1a, b). Subsequently, CCK-8, colony formation, and EdU assays demonstrated that SLC34A2 overexpression significantly promoted ESCC cell proliferation (Figure 1c-h). Furthermore, cell cycle distribution analysis revealed a significant decrease in the proportion of cells in the G0/G1 phase and an increase in the proportion of cells in the G2/M phase in SLC34A2-overexpressing cells (Figure 1i, j), indicating that SLC34A2 overexpression accelerates cell cycle progression. Xenograft tumor models further demonstrated that elevated SLC34A2 expression accelerated ESCC cell growth in vivo (Figure 1k). Furthermore, immunohistochemical staining showed that the Ki-67 proliferation index of SLC34A2-overexpressing tumors was higher than that of control tumors (Figure 1k). Thus, these results confirm that SLC34A2 upregulation promotes the growth of esophageal squamous cell carcinoma cells both in vivo and in vitro.
Figure 1. Overexpression of SLC34A2 promotes ESCC cell proliferation in vitro and in vivo. (Xu Y, et al., 2024)