Serine/threonine-protein kinase 24 is an inhibitor of gastric cancer metastasis through suppressing CDH1 gene and enhancing stemness

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Title:	Serine/threonine-protein kinase 24 is an inhibitor of gastric cancer metastasis through suppressing CDH1 gene and enhancing stemness
Authors:	Chen, Yi-Ling Wang, Chih-Yang Fang, Jung-Hua Hsu, Hui-Ping
Contributors:	Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Mol Biol & Drug Discovery Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery Natl Cheng Kung Univ, Coll Med, Lab Anim Ctr Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg
Keywords:	Gastric cancer serine/threonine-protein kinase 24 STK24 metastasis myeloid-derived suppressor cells MDSC E-cadherin CDH1 stemness CD44
Date:	2021
Issue Date:	2023-11-11 11:59:55 (UTC+8)
Publisher:	E-CENTURY PUBLISHING CORP
Abstract:	Gastric cancer patients often present with distant metastasis and advanced stages. Suppressing serine/threonine-protein kinase 24 (STK24, also known as MST3) is known to promote gastric tumorigenesis. Here, we investigated the effects from STK24 on the metastasis of gastric cancer. We used CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 technology for genetic knockout of STK24 at the genomic DNA level in human MKN45 and mouse M12 gastric cancer cells. To assess the consequences of STK24 knockdown, western blot, cell migration, and wound healing assays were conducted in vitro. An in vivo mouse model of liver metastasis was established and tested, and bioinformatics analyses were performed. The knockdown of the STK24 gene enhanced cell migration and increased liver metastasis in the mouse model of gastric cancer. STK24-silenced tumors suppressed CD4(+) T cells and enhanced the expansion of CD11b(+)Ly6C(+) myeloid-derived suppressor cells (MDSCs) and F4/80(+) macrophages in the spleen of the mice. In MKN45 cells, STK24 silencing resulted in downregulation of E-cadherin (gene CDH1, Cadherin-1, or epithelial cadherin). In 38 paired specimens of gastric adenocarcinomas and normal tissues, we examined STK24 and CDH1 expression levels via western blot; a positive correlation between the expression levels of STK24 and CDH1 was found (R-2 = 0.5507, P = 9.72 x 10(-8)). Furthermore, in Oncomine database and Kaplan-Meier plotter analysis, the loss of CDH1, increase in CCL2, and upregulation of CD44 were correlated with poor prognosis of gastric cancer patients. Our results demonstrate that knockdown of STK24 increases cell migration through suppressing CDH1 and enhancing CD44. In experimental model of metastatic gastric cancer in syngeneic inbred mice, STK24 is important for immune suppression through expansion of CD11b(+)Ly6C(+) MDSCs and F4/80(+) macrophages. We confirmed that STK24 is an inhibitor of gastric cancer metastasis.
Relation:	AM J CANCER RES, v.11, n.9, pp.4277-4293
Appears in Collections:	[Dept. of Senior Service and Health Management] Periodical Articles [Dept. of Health and Nutrition (including master's program)] Periodical Articles

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