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2 results on '"DAAM1"'

1. Wnt5a induces ROR1 and ROR2 to activate RhoA in esophageal squamous cell carcinoma cells

Author

Wu X, Yan T, Hao L, and Zhu Y

Subjects
ESCC, Invasion, Wnt5a, DAAM1, ROR, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Xuping Wu,1 Ting Yan,2 Leiyu Hao,3 Yichao Zhu3,41The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 2Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, People’s Republic of China; 3Department of Physiology, Nanjing Medical University, Nanjing 211166, People’s Republic of China; 4State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, People’s Republic of ChinaBackground: Wnt5a is a nontransforming Wnt family member and identified as an oncogenic role on cell motility of breast cancer and glioblastoma. However, Wnt5a signaling in esophageal squamous cell carcinoma (ESCC) progression remains poorly defined.Materials and methods: Immunohistochemistry assays were used to measure the Wnt5a expression in ESCC sections. We evaluated the role of receptor tyrosine kinase-like orphan receptor (ROR)1/2 and RhoA on the invasion of ESCC cells by using cell invasion assay, immunoprecipitation, immunofluorescence, and Rho activation assay.Results: Wnt5a was highly expressed in invasive ESCC tissues compared with that in noninvasive and nonmalignant tissues. In vitro assay showed that sfrp2 (Wnt5a antagonist) largely blocked the invasion but not the colony formation of KYSE410 and KYSE520 ESCC cells. Anti-ROR1 mAb and ROR2-shRNA markedly inhibited the disheveled-associated activator of morphogenesis 1 (DAAM1) activity, RhoA activity, microfilament formation and the invasion of ESCC cells. Fluorescent phalloidin staining experiment showed ROR1/ROR2, receptors of Wnt5a signaling, and regulated the reassembly of actin filaments in ESCC cells. Further experiments showed that ROR1 was strongly associated with ROR2 in KYSE410 cells. The activation of RhoA, not Rac1 or Rac2, was involved in ROR1/ROR2 signaling pathway. By using DAAM1 shRNA, we found that RhoA was downstream of DAAM1, which could be rescued by the overexpression of wild-type DAAM1. This could be further proved by a RhoA inhibitor CCG-1423 which could inhibit the invasion of ESCC cells but not DAAM1 activity.Conclusions: Wnt5a promotes ESCC cell invasion via ROR1 and ROR2 receptors and DAAM1/RhoA signaling pathway.Keywords: ESCC, invasion, Wnt5a, DAAM1, ROR

Published
2019

2. Daam1 Overexpression Promotes Gastric Cancer Progression and Regulates ERK and AKT Signaling Pathways

Author

Zhang Y, Bai X, and Li Y

Subjects
erk, daam1, akt, apoptosis, gastric cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Yue Zhang, Xue Bai, Yi Zhang, Yan Li Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Yue ZhangDepartment of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, People’s Republic of ChinaEmail zhangyue_cmu@163.comObjective: The dishevelled-associated activator of morphogenesis 1 (DAAM1) has been reported to be closely associated with human cancers. However, its involvement in human gastric cancer (GC) remains largely unexplored. This study aimed to investigate the clinical significance and biological roles of Daam1 in human GC.Methods: Daam1 protein expression was examined in 124 cases of gastric adenocarcinomas using immunohistochemistry. Daam1 plasmid and siRNA transfection were carried out in SGC7901 and AGS cell lines. CCK-8, colony formation, Annexin V/PI, JC-1 staining, and Western blotting were used to explore the biological functions and potential underlying mechanisms of Daam1 in GC cells.Results: Our results showed that Daam1 was overexpressed in GC specimens. A high Daam1 level was associated with tumor-node-metastasis (TNM) stage, T status, nodal metastasis, and poor patient survival. Analysis of the Oncomine dataset revealed upregulation of Daam1 mRNA in GC tissues. Western blot showed that Daam1 protein expression was higher in GC cell lines compared to the normal GES-1 cell line. CCK-8 and colony formation assays showed that ectopic Daam1 expression upregulated the cell growth rate and colony number in SGC-7901 cells, while Daam1 siRNA knockdown downregulated the growth rate and colony number in AGS cells. CCK-8 and Annexin V/PI apoptosis assays demonstrated that Daam1 overexpression decreased cisplatin sensitivity and downregulated cisplatin-induced apoptosis. JC1 staining showed that Daam1 overexpression upregulated, while Daam1 depletion downregulated mitochondrial membrane potential. Mechanistically, Daam1 overexpression downregulated p21 and upregulated p-ERK and p-AKT. The increased proliferation rate and decreased cisplatin sensitivity/apoptosis induced by ectopic Daam1 were reversed after treatment with AKT and ERK inhibitors.Conclusion: Taken together, our results showed that Daam1 overexpression was associated with poor prognosis and promoted malignant activity via regulation of ERK and AKT pathways in GC cells, indicating Daam1 is a malignant biomarker and potential therapeutic target in GC.Keywords: Daam1, ERK, AKT, apoptosis, gastric cancer

Published
2021

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