# SMARCD3 Overexpression Promotes Epithelial–Mesenchymal Transition in Gastric Cancer

## TL;DR

This study shows that high levels of SMARCD3 in gastric cancer cells are linked to worse survival and increased cancer spread, making it a potential treatment target.

## Contribution

The study identifies SMARCD3 overexpression as a novel driver of EMT and poor prognosis in gastric cancer.

## Key findings

- SMARCD3 overexpression correlates with poorer survival in gastric cancer patients (HR 2.16, p < 0.001).
- SMARCD3 depletion reduces cancer cell proliferation, migration, and EMT markers.
- SMARCD3 overexpression activates AKT, ERK, β-catenin, and PI3Kp85 signaling pathways in gastric cancer cells.

## Abstract

This study explores SMARCD3’s role in gastric cancer, focusing on its elevated expression in signet ring cell (SRC) versus well-differentiated (WD) groups. Elevated SMARCD3 levels in SRC correlated with poorer survival outcomes (HR 2.16, p < 0.001), as shown by Kaplan–Meier analysis. Functional assays involving SMARCD3 knock-in and knock-out highlighted that its depletion reduces cell proliferation, migration, invasion, and EMT marker expression, while overexpression increases cell irregularity and area (p < 0.001). Further investigations into signaling pathways revealed that SMARCD3 overexpression boosts p-AKT-S473 and p-ERK levels in MKN-74 cells and β-catenin and PI3Kp85 activities in KATO III cells. Conversely, its knock-out decreases these activities in SNU 601 cells. These results suggest that SMARCD3′s overexpression could serve as a negative prognostic marker and a potential target for gastric cancer therapy.

This study investigates the role of SMARCD3 in gastric cancer by comparing its expression in signet ring cell (SRC) and well-differentiated (WD) groups within gastric cancer cell lines and tissues. We observed elevated SMARCD3 levels in the SRC group compared to the WD group. Functional analysis was conducted through both SMARCD3 knock-in and knock-out methods. Kaplan–Meier survival analysis indicated that higher SMARCD3 expression correlates with poorer overall survival in gastric cancer patients (HR 2.16, p < 0.001). SMARCD3 knock-out cells showed decreased proliferation, migration, invasion, and expression of epithelial–mesenchymal transition (EMT) markers, contrasting with results from temporary and stable SMARCD3 overexpression experiments, which demonstrated increased cell area and irregularity (p < 0.001). Further analysis revealed that SMARCD3 overexpression in MKN-74 cells significantly enhanced p-AKT-S473 and p-ERK levels (p < 0.05), and in KATO III cells, it increased β-catenin and PI3Kp85 activities (p < 0.05). Conversely, these activities decreased in SNU 601 cells following SMARCD3 depletion. The study concludes that SMARCD3 overexpression may serve as a negative prognostic marker and a potential therapeutic target in gastric cancer treatment due to its role in promoting EMT.