Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01041/full |
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| author | Meng-Ling Yuan Pei Li Zi-Hao Xing Jin-Ming Di Hui Liu An-Kui Yang Xi-Jun Lin Qi-Wei Jiang Yang Yang Jia-Rong Huang Kun Wang Meng-Ning Wei Yao Li Jin Ye Zhi Shi |
| author_facet | Meng-Ling Yuan Pei Li Zi-Hao Xing Jin-Ming Di Hui Liu An-Kui Yang Xi-Jun Lin Qi-Wei Jiang Yang Yang Jia-Rong Huang Kun Wang Meng-Ning Wei Yao Li Jin Ye Zhi Shi |
| author_sort | Meng-Ling Yuan |
| collection | DOAJ |
| description | WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in LSCC tissues compared with adjacent normal tissues. Importantly, overexpression of WEE1 was correlated with T stages, lymph node metastasis, clinical stages and poor prognosis of LSCC patients. Furthermore, inhibition of WEE1 by MK-1775 induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular reactive oxygen species (ROS) levels in LSCC cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse MK-1775-induced ROS accumulation and cell apoptosis in LSCC cells. MK-1775 also inhibited the growth of LSCC xenografts in nude mice. Altogether, these findings suggest that WEE1 is a potential therapeutic target in LSCC, and inhibition of WEE1 is the prospective strategy for LSCC therapy. |
| first_indexed | 2024-12-24T13:03:55Z |
| format | Article |
| id | doaj.art-f39462d6d8d64390b67031c4281c9589 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-24T13:03:55Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f39462d6d8d64390b67031c4281c95892022-12-21T16:54:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-09-01910.3389/fphar.2018.01041407628Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell CarcinomaMeng-Ling Yuan0Pei Li1Zi-Hao Xing2Jin-Ming Di3Hui Liu4An-Kui Yang5Xi-Jun Lin6Qi-Wei Jiang7Yang Yang8Jia-Rong Huang9Kun Wang10Meng-Ning Wei11Yao Li12Jin Ye13Zhi Shi14Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDivision of Pulmonary and Critical Care, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaWEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in LSCC tissues compared with adjacent normal tissues. Importantly, overexpression of WEE1 was correlated with T stages, lymph node metastasis, clinical stages and poor prognosis of LSCC patients. Furthermore, inhibition of WEE1 by MK-1775 induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular reactive oxygen species (ROS) levels in LSCC cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse MK-1775-induced ROS accumulation and cell apoptosis in LSCC cells. MK-1775 also inhibited the growth of LSCC xenografts in nude mice. Altogether, these findings suggest that WEE1 is a potential therapeutic target in LSCC, and inhibition of WEE1 is the prospective strategy for LSCC therapy.https://www.frontiersin.org/article/10.3389/fphar.2018.01041/fulllaryngeal squamous cell carcinomaWEE1MK-1775cell cycleapoptosisreactive oxygen species |
| spellingShingle | Meng-Ling Yuan Pei Li Zi-Hao Xing Jin-Ming Di Hui Liu An-Kui Yang Xi-Jun Lin Qi-Wei Jiang Yang Yang Jia-Rong Huang Kun Wang Meng-Ning Wei Yao Li Jin Ye Zhi Shi Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma Frontiers in Pharmacology laryngeal squamous cell carcinoma WEE1 MK-1775 cell cycle apoptosis reactive oxygen species |
| title | Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma |
| title_full | Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma |
| title_fullStr | Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma |
| title_full_unstemmed | Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma |
| title_short | Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma |
| title_sort | inhibition of wee1 suppresses the tumor growth in laryngeal squamous cell carcinoma |
| topic | laryngeal squamous cell carcinoma WEE1 MK-1775 cell cycle apoptosis reactive oxygen species |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01041/full |
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