Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo
Our previous studies have demonstrated that human papillomavirus (HPV)-16 E7 oncoprotein promoted epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells. Moreover, recent studies have found that exosomes can mediate EMT of NSCLC cells and epidermal growth factor receptor...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15384047.2022.2133332 |
| _version_ | 1797404058512785408 |
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| author | Zhiyuan Zhou Xiaofeng Wu Riming Zhan Xiangyong Li Dazhao Cheng Li Chen Tianyu Wang Hua Yu Guihong Zhang Xudong Tang |
| author_facet | Zhiyuan Zhou Xiaofeng Wu Riming Zhan Xiangyong Li Dazhao Cheng Li Chen Tianyu Wang Hua Yu Guihong Zhang Xudong Tang |
| author_sort | Zhiyuan Zhou |
| collection | DOAJ |
| description | Our previous studies have demonstrated that human papillomavirus (HPV)-16 E7 oncoprotein promoted epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells. Moreover, recent studies have found that exosomes can mediate EMT of NSCLC cells and epidermal growth factor receptor (EGFR) is related to the progression of NSCLC. Here, we further investigated the role of exosomal EGFR in HPV-16 E7-induced EMT of NSCLC cells. Our results showed that the exosomes derived from the stable HPV-16 E7-overexpressing A549 and NCI-H460 NSCLC cells (E7 Exo) significantly increased migration, invasion, and proliferation abilities of NSCLC cells as compared with the exosomes derived from empty vector-infected NSCLC cells (ev Exo). Moreover, both in vitro and in vivo results demonstrated that E7 Exo dramatically enhanced EMT of NSCLC cells and promoted the growth of subcutaneous NSCLC xenografts. Additionally, HPV-16 E7 enhanced the expression of EGFR and p-EGFR in both NSCLC cells and exosomes. Furthermore, the inhibition of EGFR activation or exosome secretion suppressed E7 Exo-induced migration, invasion, and EMT of NSCLC. Moreover, 12 kinds of differentially expressed miRNAs between E7 Exo and ev Exo (fold change≥2, P ≤ .05) were screened out, of which 7 miRNAs were up-regulated while 5 miRNAs were down-regulated in A549 E7 Exo. Taken together, our findings suggest that exosomal EGFR is involved in HPV-16 E7-induced EMT of NSCLC cells, which may play a key role in the progression of HPV-related NSCLC. |
| first_indexed | 2024-03-09T02:47:37Z |
| format | Article |
| id | doaj.art-94ee608f4a07435aaa805fe54a37025c |
| institution | Directory Open Access Journal |
| issn | 1538-4047 1555-8576 |
| language | English |
| last_indexed | 2024-03-09T02:47:37Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj.art-94ee608f4a07435aaa805fe54a37025c2023-12-05T15:58:14ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762022-12-0123111310.1080/15384047.2022.21333322133332Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivoZhiyuan Zhou0Xiaofeng Wu1Riming Zhan2Xiangyong Li3Dazhao Cheng4Li Chen5Tianyu Wang6Hua Yu7Guihong Zhang8Xudong Tang9Guangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityGuangdong Medical UniversityOur previous studies have demonstrated that human papillomavirus (HPV)-16 E7 oncoprotein promoted epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells. Moreover, recent studies have found that exosomes can mediate EMT of NSCLC cells and epidermal growth factor receptor (EGFR) is related to the progression of NSCLC. Here, we further investigated the role of exosomal EGFR in HPV-16 E7-induced EMT of NSCLC cells. Our results showed that the exosomes derived from the stable HPV-16 E7-overexpressing A549 and NCI-H460 NSCLC cells (E7 Exo) significantly increased migration, invasion, and proliferation abilities of NSCLC cells as compared with the exosomes derived from empty vector-infected NSCLC cells (ev Exo). Moreover, both in vitro and in vivo results demonstrated that E7 Exo dramatically enhanced EMT of NSCLC cells and promoted the growth of subcutaneous NSCLC xenografts. Additionally, HPV-16 E7 enhanced the expression of EGFR and p-EGFR in both NSCLC cells and exosomes. Furthermore, the inhibition of EGFR activation or exosome secretion suppressed E7 Exo-induced migration, invasion, and EMT of NSCLC. Moreover, 12 kinds of differentially expressed miRNAs between E7 Exo and ev Exo (fold change≥2, P ≤ .05) were screened out, of which 7 miRNAs were up-regulated while 5 miRNAs were down-regulated in A549 E7 Exo. Taken together, our findings suggest that exosomal EGFR is involved in HPV-16 E7-induced EMT of NSCLC cells, which may play a key role in the progression of HPV-related NSCLC.http://dx.doi.org/10.1080/15384047.2022.2133332exosomesegfrhpv-16 e7emtnsclc |
| spellingShingle | Zhiyuan Zhou Xiaofeng Wu Riming Zhan Xiangyong Li Dazhao Cheng Li Chen Tianyu Wang Hua Yu Guihong Zhang Xudong Tang Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo Cancer Biology & Therapy exosomes egfr hpv-16 e7 emt nsclc |
| title | Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo |
| title_full | Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo |
| title_fullStr | Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo |
| title_full_unstemmed | Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo |
| title_short | Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo |
| title_sort | exosomal epidermal growth factor receptor is involved in hpv 16 e7 induced epithelial mesenchymal transition of non small cell lung cancer cells a driver of signaling in vivo |
| topic | exosomes egfr hpv-16 e7 emt nsclc |
| url | http://dx.doi.org/10.1080/15384047.2022.2133332 |
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