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PTEN downregulates WD repeat-containing protein 66 in salivary adenoid cystic carcinoma

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单位: [1]Laboratory of Precision Oncology, China Medical University School of Pharmacy, Shenyang, Liaoning 110122, P.R. China [2]Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA [3]Department of Oral Pathology, Dental School, Dalian Medical University [4]Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044 [5]Department of Oral Pathology, 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai Key Laboratory of Stomatology, Shanghai 200011 [6]Department of Radiation Oncology,China‑Japan Friendship Hospital, Beijing 100029 [7]Department of Surgical Oncology,The First Affiliated Hospital of China Medical University [8]Department of Oral Pathology, Dental School, China Medical University,Shenyang, Liaoning 110001, P.R. China
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关键词: salivary adenoid cystic carcinoma WD repeat-containing protein 66 phosphatase and tensin homolog epithelial-mesenchymal transition

摘要:
Salivary adenoid cystic carcinoma (SACC) is one of the most common types of salivary gland cancer that causes substantial morbidity and mortality. Despite the substantial health burden of SACC, the molecular mechanisms underlying its development and progression remain poorly understood. We previously reported the loss of phosphatase and tensin homolog (PTEN) expression to be common among SACC tumors, and the PTEN deficiency to be correlated with enrichment of epithelial-mesenchymal transition (EMT) genes based on expression array analysis. The aim of the present study was to investigate further the functional function of WD repeat-containing protein 66 (WDR66), one of the enriched EMT genes, in the context of PTEN deficiency and SACC pathogenesis. WDR66 was identified to be required to maintain the EMT phenotype and the expression of cancer stem cell genes in the context of PTEN deficiency. Furthermore, knockdown of WDR66 decreased cellular proliferation, migration and invasion. Finally, WDR66 expression was identified to be inversely associated with PTEN expression and negatively correlated with the overall survival of patients with SACC. Collectively, the results of the present study revealed a novel function of WDR66 in mediating the progression of PTEN-deficient SACCs, thereby suggesting WDR66 inhibition to be a potential therapeutic approach towards successful management of SACC disease progression, particularly against tumors with decreased PTEN expression levels.

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出版当年[2018]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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出版当年[2017]版:
Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

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第一作者单位: [1]Laboratory of Precision Oncology, China Medical University School of Pharmacy, Shenyang, Liaoning 110122, P.R. China [2]Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA
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通讯机构: [1]Laboratory of Precision Oncology, China Medical University School of Pharmacy, Shenyang, Liaoning 110122, P.R. China [2]Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO 80045, USA [3]Department of Oral Pathology, Dental School, Dalian Medical University [8]Department of Oral Pathology, Dental School, China Medical University,Shenyang, Liaoning 110001, P.R. China [*1]Department of Oral Pathology, Dental School, China Medical University, 92 Bei'er Road, Shenyang, Liaoning 110001, P.R. China [*2]Department of Otolaryngology, University of Colorado School of Medicine, 12700 E 19th Avenue, Aurora, CO 80045, USA
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