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1. FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer

Author

Hu, Xiaoling, Zhai, Yuanfang, Kong, Pengzhou, Cui, Heyang, Yan, Ting, Yang, Jian, Qian, Yu, Ma, Yanchun, Wang, Fang, Li, Hongyi, Cheng, Caixia, Zhang, Ling, Jia, Zhiwu, Li, Yaoping, Yang, Bin, Xu, Enwei, Wang, Juan, Yang, Jie, Bi, Yanghui, Chang, Lu, Wang, Yi, Zhang, Yingchun, Song, Bin, Li, Guodong, Shi, Ruyi, Liu, Jing, Zhang, Mingsheng, Cheng, Xiaolong, and Cui, Yongping

Published
2017
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2. Corrigendum to “FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer” [Canc. Lett. 397 (2017) 83–93]

Author

Hu, Xiaoling, primary, Zhai, Yuanfang, additional, Kong, Pengzhou, additional, Cui, Heyang, additional, Yan, Ting, additional, Yang, Jian, additional, Qian, Yu, additional, Ma, Yanchun, additional, Wang, Fang, additional, Li, Hongyi, additional, Cheng, Caixia, additional, Zhang, Ling, additional, Jia, Zhiwu, additional, Li, Yaoping, additional, Yang, Bin, additional, Xu, Enwei, additional, Wang, Juan, additional, Yang, Jie, additional, Bi, Yanghui, additional, Chang, Lu, additional, Wang, Yi, additional, Zhang, Yingchun, additional, Song, Bin, additional, Li, Guodong, additional, Shi, Ruyi, additional, Liu, Jing, additional, Zhang, Mingsheng, additional, Cheng, Xiaolong, additional, and Cui, Yongping, additional

Published
2020
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3. Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Author

Zhang, Ling, primary, Zhou, Yong, additional, Cheng, Caixia, additional, Cui, Heyang, additional, Cheng, Le, additional, Kong, Pengzhou, additional, Wang, Jiaqian, additional, Li, Yin, additional, Chen, Wenliang, additional, Song, Bin, additional, Wang, Fang, additional, Jia, Zhiwu, additional, Li, Lin, additional, Li, Yaoping, additional, Yang, Bin, additional, Liu, Jing, additional, Shi, Ruyi, additional, Bi, Yanghui, additional, Zhang, Yanyan, additional, Wang, Juan, additional, Zhao, Zhenxiang, additional, Hu, Xiaoling, additional, Yang, Jie, additional, Li, Hongyi, additional, Gao, Zhibo, additional, Chen, Gang, additional, Huang, Xuanlin, additional, Yang, Xukui, additional, Wan, Shengqing, additional, Chen, Chao, additional, Li, Bin, additional, Tan, Yongkai, additional, Chen, Longyun, additional, He, Minghui, additional, Xie, Sha, additional, Li, Xiangchun, additional, Zhuang, Xuehan, additional, Wang, Mengyao, additional, Xia, Zhi, additional, Luo, Longhai, additional, Ma, Jie, additional, Dong, Bing, additional, Zhao, Jiuzhou, additional, Song, Yongmei, additional, Ou, Yunwei, additional, Li, Enming, additional, Xu, Liyan, additional, Wang, Jinfen, additional, Xi, Yanfeng, additional, Li, Guodong, additional, Xu, Enwei, additional, Liang, Jianfang, additional, Yang, Xiaofeng, additional, Guo, Jiansheng, additional, Chen, Xing, additional, Zhang, Yanbo, additional, Li, Qingshan, additional, Liu, Lixin, additional, Li, Yingrui, additional, Zhang, Xiuqing, additional, Yang, Huanming, additional, Lin, Dongxin, additional, Cheng, Xiaolong, additional, Guo, Yongjun, additional, Wang, Jun, additional, Zhan, Qimin, additional, and Cui, Yongping, additional

Published
2020
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5. Mps1 is associated with the BRAFV600E mutation but does not rely on the classic RAS/RAF/MEK/ERK signaling pathway in thyroid carcinoma

Author

Li, Yike, primary, Zhang, Yanyan, additional, Xiao, Shuaishuai, additional, Kong, Pengzhou, additional, Cheng, Caixia, additional, Shi, Ruyi, additional, Wang, Fang, additional, Zhang, Ling, additional, Wang, Juan, additional, Jia, Zhiwu, additional, Wu, Shuai, additional, Liu, Yun, additional, Guo, Jiansheng, additional, Cheng, Xiaolong, additional, Cui, Yongping, additional, and Liu, Jing, additional

Published
2018
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6. WITHDRAWN: Potential therapeutic targets screening for esophageal squamous cell carcinoma via combined analysis of genomic sequencing data and target pharmacophore database

Author

Zhang, Ling, primary, Liu, Feng, additional, Bi, Yanghui, additional, Cui, Heyang, additional, Kong, Pengzhou, additional, Li, Jiayi, additional, Song, Bin, additional, Zou, Binbin, additional, Cheng, Caixia, additional, Yan, Ting, additional, Yang, Jian, additional, Qian, Yu, additional, Ma, Yanchun, additional, Wang, Fang, additional, Li, Hongyi, additional, Jia, Zhiwu, additional, Hu, Xiaoling, additional, Yang, Bin, additional, Xu, Enwei, additional, Li, Yaoping, additional, Wang, Juan, additional, Yang, Jie, additional, Zhai, Yuanfang, additional, Liu, Yiqian, additional, Chang, Lu, additional, Wang, Yi, additional, Zhang, Yingchun, additional, Shi, Ruyi, additional, Jia, Junmei, additional, Liu, Jing, additional, Cheng, Xiaolong, additional, and Cui, Yongping, additional

Published
2018
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7. High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC

Author

Yang, Jie, primary, Kong, Pengzhou, additional, Yang, Jian, additional, Jia, Zhiwu, additional, Hu, Xiaoling, additional, Wang, Zianyi, additional, Cui, Heyang, additional, Bi, Yanghui, additional, Qian, Yu, additional, Li, Hongyi, additional, Wang, Fang, additional, Yang, Bin, additional, Yan, Ting, additional, Ma, Yanchun, additional, Zhang, Ling, additional, Cheng, Caixia, additional, Song, Bin, additional, Li, Yaoping, additional, Xu, Enwei, additional, Liu, Haiyan, additional, Gao, Wei, additional, Wang, Juan, additional, Liu, Yiqian, additional, Zhai, Yuanfang, additional, Chang, Lu, additional, Wang, Yi, additional, Zhang, Yingchun, additional, Shi, Ruyi, additional, Liu, Jing, additional, Wang, Qi, additional, Cheng, Xiaolong, additional, and Cui, Yongping, additional

Published
2018
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8. WITHDRAWN: EP300 promotes tumor development and correlates with poor prognosis in esophageal squamous carcinoma

Author

Bi, Yanghui, primary, Zhang, Ling, additional, Cui, Heyang, additional, Kong, Pengzhou, additional, Yan, Ting, additional, Li, Jiayi, additional, Wang, Zianyi, additional, Cheng, Caixia, additional, Song, Bin, additional, Yang, Bin, additional, Xu, Enwei, additional, Yang, Jie, additional, Hu, Xiaoling, additional, Shi, Ruyi, additional, Qian, Yu, additional, Wang, Fang, additional, Li, Hongyi, additional, Jia, Zhiwu, additional, Ma, Yanchun, additional, Yang, Jian, additional, Li, Yike, additional, Wang, Juan, additional, Liu, Yiqian, additional, Zhai, Yuanfang, additional, Chang, Lu, additional, Wang, Yi, additional, Zhang, Yingchun, additional, Liu, Feng, additional, Liu, Haiyan, additional, Zhang, Yanyan, additional, Liu, Jing, additional, Cheng, Xiaolong, additional, and Cui, Yongping, additional

Published
2017
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9. The macro-evolutionary events in esophageal squamous cell carcinoma

Author

Yang, Bin, primary, Yan, Ting, additional, Cui, Heyang, additional, Xu, Enwei, additional, Ma, Yanchun, additional, Cheng, Caixia, additional, Zhang, Ling, additional, Kong, Pengzhou, additional, Wang, Fang, additional, Qian, Yu, additional, Yang, Jian, additional, Li, Yaoping, additional, Li, Hongyi, additional, Bi, Yanghui, additional, Hu, Xiaoling, additional, Wang, Juan, additional, Song, Bin, additional, Yang, Jie, additional, Gao, Wei, additional, Liu, Jing, additional, Zou, Binbin, additional, Shi, Ruyi, additional, Zhang, Yanyan, additional, Liu, Haiyan, additional, Liu, Yiqian, additional, Zhai, Yuanfang, additional, Chang, Lu, additional, Wang, Yi, additional, Zhang, Yingchun, additional, Jia, Zhiwu, additional, Chen, Xing, additional, Xi, Yanfeng, additional, Li, Guodong, additional, Liang, Jianfang, additional, Guo, Jiansheng, additional, Guo, Shiping, additional, Zhang, Rongsheng, additional, Cheng, Xiaolong, additional, and Cui, Yongping, additional

Published
2017
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10. Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma

Author

Cheng, Caixia, primary, Zhou, Yong, additional, Li, Hongyi, additional, Xiong, Teng, additional, Li, Shuaicheng, additional, Bi, Yanghui, additional, Kong, Pengzhou, additional, Wang, Fang, additional, Cui, Heyang, additional, Li, Yaoping, additional, Fang, Xiaodong, additional, Yan, Ting, additional, Li, Yike, additional, Wang, Juan, additional, Yang, Bin, additional, Zhang, Ling, additional, Jia, Zhiwu, additional, Song, Bin, additional, Hu, Xiaoling, additional, Yang, Jie, additional, Qiu, Haile, additional, Zhang, Gehong, additional, Liu, Jing, additional, Xu, Enwei, additional, Shi, Ruyi, additional, Zhang, Yanyan, additional, Liu, Haiyan, additional, He, Chanting, additional, Zhao, Zhenxiang, additional, Qian, Yu, additional, Rong, Ruizhou, additional, Han, Zhiwei, additional, Zhang, Yanlin, additional, Luo, Wen, additional, Wang, Jiaqian, additional, Peng, Shaoliang, additional, Yang, Xukui, additional, Li, Xiangchun, additional, Li, Lin, additional, Fang, Hu, additional, Liu, Xingmin, additional, Ma, Li, additional, Chen, Yunqing, additional, Guo, Shiping, additional, Chen, Xing, additional, Xi, Yanfeng, additional, Li, Guodong, additional, Liang, Jianfang, additional, Yang, Xiaofeng, additional, Guo, Jiansheng, additional, Jia, JunMei, additional, Li, Qingshan, additional, Cheng, Xiaolong, additional, Zhan, Qimin, additional, and Cui, Yongping, additional

Published
2016
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11. Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma

Author

Cheng, Caixia, primary, Cui, Heyang, additional, Zhang, Ling, additional, Jia, Zhiwu, additional, Song, Bin, additional, Wang, Fang, additional, Li, Yaoping, additional, Liu, Jing, additional, Kong, Pengzhou, additional, Shi, Ruyi, additional, Bi, Yanghui, additional, Yang, Bin, additional, Wang, Juan, additional, Zhao, Zhenxiang, additional, Zhang, Yanyan, additional, Hu, Xiaoling, additional, Yang, Jie, additional, He, Chanting, additional, Zhao, Zhiping, additional, Wang, Jinfen, additional, Xi, Yanfeng, additional, Xu, Enwei, additional, Li, Guodong, additional, Guo, Shiping, additional, Chen, Yunqing, additional, Yang, Xiaofeng, additional, Chen, Xing, additional, Liang, Jianfang, additional, Guo, Jiansheng, additional, Cheng, Xiaolong, additional, Wang, Chuangui, additional, Zhan, Qimin, additional, and Cui, Yongping, additional

Published
2016
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12. Mps1 is associated with the BRAFV600E mutation but does not rely on the classic RAS/RAF/MEK/ERK signaling pathway in thyroid carcinoma.

Author

Li, Yike, Zhang, Yanyan, Xiao, Shuaishuai, Kong, PENgzhou, ChENg, Caixia, Shi, Ruyi, Wang, Fang, Zhang, Ling, Wang, Juan, Jia, Zhiwu, Wu, Shuai, Liu, Yun, Guo, JianshENg, ChENg, Xiaolong, Cui, Yongping, and Liu, Jing

Subjects
THYROID cancer, CARCINOMA, SERINE/THREONINE kinases, CHROMOSOMES, IMMUNOHISTOCHEMISTRY
Abstract

In previous studies, the B‑Raf proto‑oncogene, serine/threonine kinase (BRAF)V600E mutation has been identified in multiple malignant tumors. BRAFV600E has been revealed to contribute to tumorigenesis by the activation of phospho‑mitogen‑activated protein kinases (MAPKs) and their downstream Monopolar spindle 1 (Mps1), leading to chromosome euploidy and tumor development. In the present study, the presence of phospho‑MAPK and Mps1 in 161 thyroid carcinoma cases with complete clinical parameters was analyzed by immunohistochemistry, and the BRAF mutation was detected by polymerase chain reaction‑direct sequencing. It was revealed that BRAFV600E was present in ~34% of thyroid cancer cases and was associated with age, clinical tumor stage and lymph node stage. However, the association of BRAFV600E with overall survival was not statistically significant. The expression of Mps1 was significantly increased in tumor tissues with BRAFV600E, however, this did not affect the expression of phospho‑MAPK in thyroid carcinomas. Collectively, the results of the present study suggested that BRAFV600E may regulate the expression of Mps1 in MAP kinase independent ways in thyroid carcinoma. Therefore, Mps1 expression is associated with BRAFV600E while the upstream signaling of phospho‑MAPK has no relevance. The specific mechanisms of BRAFV600E and the unknown pathway associated with Mps1 exhibit potential for further study, and provide a theoretical basis for the molecular treatment of thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Published
2018
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13. Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Author

Zhang, Ling, primary, Zhou, Yong, additional, Cheng, Caixia, additional, Cui, Heyang, additional, Cheng, Le, additional, Kong, Pengzhou, additional, Wang, Jiaqian, additional, Li, Yin, additional, Chen, Wenliang, additional, Song, Bin, additional, Wang, Fang, additional, Jia, Zhiwu, additional, Li, Lin, additional, Li, Yaoping, additional, Yang, Bin, additional, Liu, Jing, additional, Shi, Ruyi, additional, Bi, Yanghui, additional, Zhang, Yanyan, additional, Wang, Juan, additional, Zhao, Zhenxiang, additional, Hu, Xiaoling, additional, Yang, Jie, additional, Li, Hongyi, additional, Gao, Zhibo, additional, Chen, Gang, additional, Huang, Xuanlin, additional, Yang, Xukui, additional, Wan, Shengqing, additional, Chen, Chao, additional, Li, Bin, additional, Tan, Yongkai, additional, Chen, Longyun, additional, He, Minghui, additional, Xie, Sha, additional, Li, Xiangchun, additional, Zhuang, Xuehan, additional, Wang, Mengyao, additional, Xia, Zhi, additional, Luo, Longhai, additional, Ma, Jie, additional, Dong, Bing, additional, Zhao, Jiuzhou, additional, Song, Yongmei, additional, Ou, Yunwei, additional, Li, Enming, additional, Xu, Liyan, additional, Wang, Jinfen, additional, Xi, Yanfeng, additional, Li, Guodong, additional, Xu, Enwei, additional, Liang, Jianfang, additional, Yang, Xiaofeng, additional, Guo, Jiansheng, additional, Chen, Xing, additional, Zhang, Yanbo, additional, Li, Qingshan, additional, Liu, Lixin, additional, Li, Yingrui, additional, Zhang, Xiuqing, additional, Yang, Huanming, additional, Lin, Dongxin, additional, Cheng, Xiaolong, additional, Guo, Yongjun, additional, Wang, Jun, additional, Zhan, Qimin, additional, and Cui, Yongping, additional

Published
2015
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14. Mutually exclusive mutations inNOTCH1andPIK3CAassociated with clinical prognosis and chemotherapy responses of esophageal squamous cell carcinoma in China

Author

Song, Bin, primary, Cui, Heyang, additional, Li, Yaoping, additional, Cheng, Caixia, additional, Yang, Bin, additional, Wang, Fang, additional, Kong, Pengzhou, additional, Li, Hongyi, additional, Zhang, Ling, additional, Jia, Zhiwu, additional, Bi, Yanghui, additional, Wang, Jiaqian, additional, Zhou, Yong, additional, Liu, Jing, additional, Wang, Juan, additional, Zhao, Zhenxiang, additional, Zhang, Yanyan, additional, Hu, Xiaoling, additional, Shi, Ruyi, additional, Yang, Jie, additional, Liu, Haiyan, additional, Yan, Ting, additional, Li, Yike, additional, Xu, Enwei, additional, Qian, Yu, additional, Xi, Yanfeng, additional, Guo, Shiping, additional, Chen, Yunqing, additional, Wang, Jinfen, additional, Li, Guodong, additional, Liang, Jianfang, additional, Jia, Junmei, additional, Chen, Xing, additional, Guo, Jiansheng, additional, Wang, Tong, additional, Zhang, Yanbo, additional, Li, Qingshan, additional, Wang, Chuangui, additional, Cheng, Xiaolong, additional, Zhan, Qimin, additional, and Cui, Yongping, additional

Published
2015
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15. Artesunate altered cellular mechanical properties leading to deregulation of cell proliferation and migration in esophageal squamous cell carcinoma

Author

SHI, RUYI, primary, CUI, HEYANG, additional, BI, YANGHUI, additional, HUANG, XUN, additional, SONG, BIN, additional, CHENG, CAIXIA, additional, ZHANG, LING, additional, LIU, JING, additional, HE, CHANTING, additional, WANG, FANG, additional, JIA, ZHIWU, additional, YANG, BIN, additional, WANG, JUAN, additional, DONG, JINYAO, additional, DU, ZHIJIE, additional, XIAO, SHUAISHUAI, additional, CUI, YONGPING, additional, and CHENG, XIAOLONG, additional

Published
2015
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16. Mps1 is associated with the BRAF V600E mutation but does not rely on the classic RAS/RAF/MEK/ERK signaling pathway in thyroid carcinoma.

Author

Li Y, Zhang Y, Xiao S, Kong P, Cheng C, Shi R, Wang F, Zhang L, Wang J, Jia Z, Wu S, Liu Y, Guo J, Cheng X, Cui Y, and Liu J

Abstract

In previous studies, the B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation has been identified in multiple malignant tumors. BRAF V600E has been revealed to contribute to tumorigenesis by the activation of phospho-mitogen-activated protein kinases (MAPKs) and their downstream Monopolar spindle 1 (Mps1), leading to chromosome euploidy and tumor development. In the present study, the presence of phospho-MAPK and Mps1 in 161 thyroid carcinoma cases with complete clinical parameters was analyzed by immunohistochemistry, and the BRAF mutation was detected by polymerase chain reaction-direct sequencing. It was revealed that BRAF V600E was present in ~34% of thyroid cancer cases and was associated with age, clinical tumor stage and lymph node stage. However, the association of BRAF V600E with overall survival was not statistically significant. The expression of Mps1 was significantly increased in tumor tissues with BRAF V600E , however, this did not affect the expression of phospho-MAPK in thyroid carcinomas. Collectively, the results of the present study suggested that BRAF V600E may regulate the expression of Mps1 in MAP kinase independent ways in thyroid carcinoma. Therefore, Mps1 expression is associated with BRAF V600E while the upstream signaling of phospho-MAPK has no relevance. The specific mechanisms of BRAF V600E and the unknown pathway associated with Mps1 exhibit potential for further study, and provide a theoretical basis for the molecular treatment of thyroid carcinoma.

Published
2018
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17. Mutually exclusive mutations in NOTCH1 and PIK3CA associated with clinical prognosis and chemotherapy responses of esophageal squamous cell carcinoma in China.

Author

Song B, Cui H, Li Y, Cheng C, Yang B, Wang F, Kong P, Li H, Zhang L, Jia Z, Bi Y, Wang J, Zhou Y, Liu J, Wang J, Zhao Z, Zhang Y, Hu X, Shi R, Yang J, Liu H, Yan T, Li Y, Xu E, Qian Y, Xi Y, Guo S, Chen Y, Wang J, Li G, Liang J, Jia J, Chen X, Guo J, Wang T, Zhang Y, Li Q, Wang C, Cheng X, Zhan Q, and Cui Y

Subjects
Aged, Apoptosis drug effects, Biomarkers, Tumor genetics, Blotting, Western, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Cell Proliferation drug effects, China, Cisplatin administration & dosage, Class I Phosphatidylinositol 3-Kinases, Esophageal Neoplasms drug therapy, Esophageal Neoplasms genetics, Female, Fluorouracil administration & dosage, Follow-Up Studies, Genomics methods, Humans, Immunoenzyme Techniques, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Grading, Neoplasm Invasiveness, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local genetics, Neoplasm Staging, Paclitaxel administration & dosage, Prognosis, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Tumor Cells, Cultured, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Squamous Cell secondary, Esophageal Neoplasms pathology, Mutation genetics, Neoplasm Recurrence, Local pathology, Phosphatidylinositol 3-Kinases genetics, Receptor, Notch1 genetics
Abstract

Background: Recurrent genetic abnormalities that correlate with clinical features could be used to determine patients' prognosis, select treatments and predict responses to therapy. Esophageal squamous cell carcinoma (ESCC) contains genomic alterations of undefined clinical significance. We aimed to identify mutually exclusive mutations that are frequently detected in ESCCs and characterized their associations with clinical variables., Methods: We analyzed next-generation-sequencing data from 104 ESCCs from Taihang Mountain region of China; 96 pairs were selected for deep target-capture-based validation and analysis of clinical and pathology data. We used model proposed by Szczurek to identify exclusive mutations and to associate these with pathology findings. Univariate and multivariate analyses with Cox proportional hazards model were used to examine the association between mutations and overall survival and response to chemotherapy. Findings were validated in an analysis of samples from 89 patients with ESCC from Taihang Mountain., Results: We identified statistically significant mutual exclusivity between mutations in NOTCH1 and PIK3CA in ESCC samples. Mutations in NOTCH1 were associated with well-differentiated, early-stage malignancy and less metastasis to regional lymph nodes. Nonetheless, patients with NOTCH1 mutations had shorter survival times than patients without NOTCH1 mutations, and failed to respond to chemotherapy. In contrast, patients with mutations in PIK3CA had better responses to chemotherapy and longer survival times than patients without PIK3CA mutations., Conclusions: In a genetic analysis of ESCCs from patients in China, we identified mutually exclusive mutations in NOTCH1 and PIK3CA. These findings might increase our understanding of ESCC development and be used as prognostic factors.

Published
2016
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18. [Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in melanoma].

Author

Zhang L, He C, Bi Y, Liu F, Cui H, Wang J, Song B, Shi R, Yang B, Wang F, Jia Z, Zhao Z, and Liu J

Subjects
Cell Line, Tumor, Humans, Melanoma genetics, Mutation, Phenotype, Signal Transduction, Transfection, Cell Cycle Proteins metabolism, MAP Kinase Signaling System, Melanoma metabolism, Protein Serine-Threonine Kinases metabolism, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins B-raf metabolism
Abstract

Objective: To study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma., Methods: Melanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression., Results: In melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity. However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector., Conclusions: Based on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.

Published
2015

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