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- Title
SMARCD3 Overexpression Promotes Epithelial–Mesenchymal Transition in Gastric Cancer.
- Authors
Park, Sun Yi; Park, Ji-Ho; Yang, Jung Wook; Jung, Eun-Jung; Ju, Young-Tae; Jeong, Chi-Young; Kim, Ju-Yeon; Park, Taejin; Kim, Tae-Han; Park, Miyeong; Lee, Young-Joon; Jeong, Sang-Ho
- Abstract
Simple Summary: 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.
- Subjects
PROTEINS; STOMACH tumors; EPITHELIAL-mesenchymal transition; T-test (Statistics); CELL proliferation; DESCRIPTIVE statistics; CELLULAR signal transduction; CHI-squared test; GENE expression; KAPLAN-Meier estimator; CELL lines; IMMUNOHISTOCHEMISTRY; ONE-way analysis of variance; DATA analysis software; BIOLOGICAL assay
- Publication
Cancers, 2024, Vol 16, Issue 12, p2282
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16122282