PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway
Through facilitating DNA homologous recombination repair, PPIP5K2 has been proven to be essential for improving colorectal cancer survival in our previous research. However, its function in the tumorigenesis of NSCLC, the most common cancer and the primary cause of cancer-related death globally, is...
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MDPI AG
2024-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/3/590 |
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| author | Qi Yang Chenhui Cao Binghuo Wu Haochi Yang Tian Tan Dan Shang Chuan Xu Xiaoyi Huang |
| author_facet | Qi Yang Chenhui Cao Binghuo Wu Haochi Yang Tian Tan Dan Shang Chuan Xu Xiaoyi Huang |
| author_sort | Qi Yang |
| collection | DOAJ |
| description | Through facilitating DNA homologous recombination repair, PPIP5K2 has been proven to be essential for improving colorectal cancer survival in our previous research. However, its function in the tumorigenesis of NSCLC, the most common cancer and the primary cause of cancer-related death globally, is still unknown. Here, we initially discovered that PPIP5K2 had significant effects on proliferation of NSCLC cells through loss- and gain-of-function assays in vitro and in vivo. Moreover, PPIP5K2 is capable of regulating NSCLC cells metastasis in an EMT-dependent manner. In terms of mechanism exploration, we found that PPIP5K2 knockdown can significantly inhibit the phosphorylation of AKT/mTOR signaling pathway, whereas the overexpression of PPIP5K2 resulted in converse effects. By employing AKT signaling related agonists or antagonists, we further demonstrated that PPIP5K2 regulates NSCLC tumorigenesis partly via the AKT/mTOR pathway. In conclusion, PPIP5K2 plays a key oncogenic role in NSCLC by the activation of the AKT/mTOR signaling axis. It is anticipated that targeting PPIP5K2 might emerge as a viable therapeutic approach for NSCLC patients. |
| first_indexed | 2024-03-08T03:59:48Z |
| format | Article |
| id | doaj.art-982e2a7b637c43989d47460602037c87 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T03:59:48Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-982e2a7b637c43989d47460602037c872024-02-09T15:09:13ZengMDPI AGCancers2072-66942024-01-0116359010.3390/cancers16030590PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling PathwayQi Yang0Chenhui Cao1Binghuo Wu2Haochi Yang3Tian Tan4Dan Shang5Chuan Xu6Xiaoyi Huang7Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150001, ChinaSichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, ChinaSchool of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, ChinaBiotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150001, ChinaThrough facilitating DNA homologous recombination repair, PPIP5K2 has been proven to be essential for improving colorectal cancer survival in our previous research. However, its function in the tumorigenesis of NSCLC, the most common cancer and the primary cause of cancer-related death globally, is still unknown. Here, we initially discovered that PPIP5K2 had significant effects on proliferation of NSCLC cells through loss- and gain-of-function assays in vitro and in vivo. Moreover, PPIP5K2 is capable of regulating NSCLC cells metastasis in an EMT-dependent manner. In terms of mechanism exploration, we found that PPIP5K2 knockdown can significantly inhibit the phosphorylation of AKT/mTOR signaling pathway, whereas the overexpression of PPIP5K2 resulted in converse effects. By employing AKT signaling related agonists or antagonists, we further demonstrated that PPIP5K2 regulates NSCLC tumorigenesis partly via the AKT/mTOR pathway. In conclusion, PPIP5K2 plays a key oncogenic role in NSCLC by the activation of the AKT/mTOR signaling axis. It is anticipated that targeting PPIP5K2 might emerge as a viable therapeutic approach for NSCLC patients.https://www.mdpi.com/2072-6694/16/3/590PPIP5K2NSCLCproliferationEMT-dependent metastasisAKT/mTOR pathway |
| spellingShingle | Qi Yang Chenhui Cao Binghuo Wu Haochi Yang Tian Tan Dan Shang Chuan Xu Xiaoyi Huang PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway Cancers PPIP5K2 NSCLC proliferation EMT-dependent metastasis AKT/mTOR pathway |
| title | PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway |
| title_full | PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway |
| title_fullStr | PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway |
| title_full_unstemmed | PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway |
| title_short | PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway |
| title_sort | ppip5k2 facilitates proliferation and metastasis of non small lung cancer nsclc through akt signaling pathway |
| topic | PPIP5K2 NSCLC proliferation EMT-dependent metastasis AKT/mTOR pathway |
| url | https://www.mdpi.com/2072-6694/16/3/590 |
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