AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo
Adenylate kinase 2 (AK2) is a wide-spread and highly conserved protein kinase whose main function is to catalyze the exchange of nucleotide phosphate groups. In this study, we showed that AK2 regulated tumor cell metastasis in lung adenocarcinoma. Positive expression of AK2 is related to lung adenoc...
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doaj-e62503b960ea4ccd81fac938ee53e2612021-09-22T12:21:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.714365714365AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivoFangfang Cai0Fangfang Cai1Huangru Xu2Daolong Zha3Xiaoyang Wang4Ping Li5Shihui Yu6Yingying Yao7Xiaoyao Chang8Jia Chen9Yanyan Lu10Zi-Chun Hua11Zi-Chun Hua12Zi-Chun Hua13Hongqin Zhuang14The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, ChinaChangzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, ChinaThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, ChinaAdenylate kinase 2 (AK2) is a wide-spread and highly conserved protein kinase whose main function is to catalyze the exchange of nucleotide phosphate groups. In this study, we showed that AK2 regulated tumor cell metastasis in lung adenocarcinoma. Positive expression of AK2 is related to lung adenocarcinoma progression and poor survival of patients. Knockdown or knockout of AK2 inhibited, while overexpression of AK2 promoted, human lung adenocarcinoma cell migration and invasion ability. Differential proteomics results showed that AK2 might be closely related to epithelial-mesenchymal transition (EMT). Further research indicated that AK2 regulated EMT occurrence through the Smad-dependent classical signaling pathways as measured by western blot and qPCR assays. Additionally, in vivo experiments showed that AK2-knockout in human lung tumor cells reduced their EMT-like features and formed fewer metastatic nodules both in liver and in lung tissues. In conclusion, we uncover a cancer metastasis-promoting role for AK2 and provide a rationale for targeting AK2 as a potential therapeutic approach for lung cancer.https://www.frontiersin.org/articles/10.3389/fphar.2021.714365/fullAK2lung adenocarcinomaEMTtumor metastasisTGF-β |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fangfang Cai Fangfang Cai Huangru Xu Daolong Zha Xiaoyang Wang Ping Li Shihui Yu Yingying Yao Xiaoyao Chang Jia Chen Yanyan Lu Zi-Chun Hua Zi-Chun Hua Zi-Chun Hua Hongqin Zhuang |
spellingShingle |
Fangfang Cai Fangfang Cai Huangru Xu Daolong Zha Xiaoyang Wang Ping Li Shihui Yu Yingying Yao Xiaoyao Chang Jia Chen Yanyan Lu Zi-Chun Hua Zi-Chun Hua Zi-Chun Hua Hongqin Zhuang AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo Frontiers in Pharmacology AK2 lung adenocarcinoma EMT tumor metastasis TGF-β |
author_facet |
Fangfang Cai Fangfang Cai Huangru Xu Daolong Zha Xiaoyang Wang Ping Li Shihui Yu Yingying Yao Xiaoyao Chang Jia Chen Yanyan Lu Zi-Chun Hua Zi-Chun Hua Zi-Chun Hua Hongqin Zhuang |
author_sort |
Fangfang Cai |
title |
AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo |
title_short |
AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo |
title_full |
AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo |
title_fullStr |
AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo |
title_full_unstemmed |
AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo |
title_sort |
ak2 promotes the migration and invasion of lung adenocarcinoma by activating tgf-β/smad pathway in vitro and in vivo |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-09-01 |
description |
Adenylate kinase 2 (AK2) is a wide-spread and highly conserved protein kinase whose main function is to catalyze the exchange of nucleotide phosphate groups. In this study, we showed that AK2 regulated tumor cell metastasis in lung adenocarcinoma. Positive expression of AK2 is related to lung adenocarcinoma progression and poor survival of patients. Knockdown or knockout of AK2 inhibited, while overexpression of AK2 promoted, human lung adenocarcinoma cell migration and invasion ability. Differential proteomics results showed that AK2 might be closely related to epithelial-mesenchymal transition (EMT). Further research indicated that AK2 regulated EMT occurrence through the Smad-dependent classical signaling pathways as measured by western blot and qPCR assays. Additionally, in vivo experiments showed that AK2-knockout in human lung tumor cells reduced their EMT-like features and formed fewer metastatic nodules both in liver and in lung tissues. In conclusion, we uncover a cancer metastasis-promoting role for AK2 and provide a rationale for targeting AK2 as a potential therapeutic approach for lung cancer. |
topic |
AK2 lung adenocarcinoma EMT tumor metastasis TGF-β |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.714365/full |
work_keys_str_mv |
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