Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer
Abstract Background High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and cl...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1316-7 |
| _version_ | 1818455936718602240 |
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| author | Xianglin Hao Li-yun Gao Ning Zhang Hongqiang Chen Xiao Jiang Wenbin Liu Lin Ao Jia Cao Fei Han Jinyi Liu |
| author_facet | Xianglin Hao Li-yun Gao Ning Zhang Hongqiang Chen Xiao Jiang Wenbin Liu Lin Ao Jia Cao Fei Han Jinyi Liu |
| author_sort | Xianglin Hao |
| collection | DOAJ |
| description | Abstract Background High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and clinical significance of Tac2-N in lung cancer progression are still unknown. Methods Tissue microarrays of 272 lung cancer patients were constructed to assess the association of Tac2-N expression and prognosis of lung cancer patients with different clinical stages. The protein expression of Tac2-N in metastatic and non-metastatic specimens were detected by IHC. In vitro migration and invasion and in vivo nude mice metastasis model were used to evaluate the effect of Tac2-N ectopic expression on metastasis capability of lung cancer cells. The downstream signaling pathway of Tac2-N was explored using luciferase reporter assays and WB. Results The expression of Tac2-N was associated with advanced stages, but not with early stages (P = 0.513). Tac2-N expression is sharply overexpressed in metastatic tumors compared with non-metastatic tumors. In vitro and in vivo assays suggested that Tac2-N facilitated migration and invasion of lung cancer cells in vitro and promoted tumor metastasis in vivo. Mechanistically, Tac2-N increased the degradation of IκB by promoting its phosphorylation, and subsequently activated NF-κB activity by facilitating the nuclear translocation of NF-κB and stimulating the transcription of targets, MMP7 and MMP9. Notably, the C2B domain of Tac2-N was crucial for Tac2-N to activate NF-κB signal. Blockage of NF-κB by shRNA or inhibitor attenuates the function of Tac2-N in the promotion of metastasis. Conclusions Our study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer. |
| first_indexed | 2024-12-14T22:18:42Z |
| format | Article |
| id | doaj.art-5492ce411cbe4592b20c1bf980ecc044 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-14T22:18:42Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-5492ce411cbe4592b20c1bf980ecc0442022-12-21T22:45:33ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-08-0138111010.1186/s13046-019-1316-7Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancerXianglin Hao0Li-yun Gao1Ning Zhang2Hongqiang Chen3Xiao Jiang4Wenbin Liu5Lin Ao6Jia Cao7Fei Han8Jinyi Liu9Institute of Toxicology, College of Preventive Medicine, Third Military Medical UniversitySchool of Public Health, Xinxiang Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityAbstract Background High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and clinical significance of Tac2-N in lung cancer progression are still unknown. Methods Tissue microarrays of 272 lung cancer patients were constructed to assess the association of Tac2-N expression and prognosis of lung cancer patients with different clinical stages. The protein expression of Tac2-N in metastatic and non-metastatic specimens were detected by IHC. In vitro migration and invasion and in vivo nude mice metastasis model were used to evaluate the effect of Tac2-N ectopic expression on metastasis capability of lung cancer cells. The downstream signaling pathway of Tac2-N was explored using luciferase reporter assays and WB. Results The expression of Tac2-N was associated with advanced stages, but not with early stages (P = 0.513). Tac2-N expression is sharply overexpressed in metastatic tumors compared with non-metastatic tumors. In vitro and in vivo assays suggested that Tac2-N facilitated migration and invasion of lung cancer cells in vitro and promoted tumor metastasis in vivo. Mechanistically, Tac2-N increased the degradation of IκB by promoting its phosphorylation, and subsequently activated NF-κB activity by facilitating the nuclear translocation of NF-κB and stimulating the transcription of targets, MMP7 and MMP9. Notably, the C2B domain of Tac2-N was crucial for Tac2-N to activate NF-κB signal. Blockage of NF-κB by shRNA or inhibitor attenuates the function of Tac2-N in the promotion of metastasis. Conclusions Our study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer.http://link.springer.com/article/10.1186/s13046-019-1316-7Tac2-NMetastasisNF-κB signaling pathwayLung cancer |
| spellingShingle | Xianglin Hao Li-yun Gao Ning Zhang Hongqiang Chen Xiao Jiang Wenbin Liu Lin Ao Jia Cao Fei Han Jinyi Liu Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer Journal of Experimental & Clinical Cancer Research Tac2-N Metastasis NF-κB signaling pathway Lung cancer |
| title | Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer |
| title_full | Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer |
| title_fullStr | Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer |
| title_full_unstemmed | Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer |
| title_short | Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer |
| title_sort | tac2 n acts as a novel oncogene and promotes tumor metastasis via activation of nf κb signaling in lung cancer |
| topic | Tac2-N Metastasis NF-κB signaling pathway Lung cancer |
| url | http://link.springer.com/article/10.1186/s13046-019-1316-7 |
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