SMARCD3 Overexpression Promotes Epithelial-Mesenchymal Transition in Gastric Cancer

Sun Yi Park; Ji-Ho Park; Jung Wook Yang; Eun-Jung Jung; Young-Tae Ju; Chi-Young Jeong; Ju-Yeon Kim; Taejin Park; Tae-Han Kim; Miyeong Park; Young-Joon Lee; Sang-Ho Jeong

doi:10.3390/cancers16122282

SMARCD3 Overexpression Promotes Epithelial-Mesenchymal Transition in Gastric Cancer

Cancers (Basel). 2024 Jun 20;16(12):2282. doi: 10.3390/cancers16122282.

Authors

Affiliations

¹ Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea.
² Department of Pathology, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea.
³ Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea.
⁴ Department of Anesthesiology, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon 51472, Republic of Korea.

Abstract

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.

Keywords: biomarker; epithelial–mesenchymal transition; gastric neoplasm; prognosis.

Grants and funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Republic of Korean Government (NRF-2022R1F1A1063290).