Sustained expression of HPV16 E7 oncoprotein promotes p-AKT((Ser473))/p-Src((Tyr527)) signaling to drive precancerous lesions to invasive cervical cancer

doi:10.1093/carcin/bgac010

科研成果详情

题名	Sustained expression of HPV16 E7 oncoprotein promotes p-AKT((Ser473))/p-Src((Tyr527)) signaling to drive precancerous lesions to invasive cervical cancer
作者	Lin, Zhongmin1; Zhao, Yu2; Li, Qijia 2,3; Ci, Xingyuan 2,3; Ye, Xiaoxian3; Chen, Guorong1; Tu, Quanmei3; Feng, Weixu 3; Jiang, Pengfei3; Zhu, Shanli3; Xue, Xiangyang3; Saunders, Nicholas A.4; Zhang, Lifang3,6; Zhu, Xueqiong2; Zhao, Kong-Nan2,3,5
发表日期	2022-06-04
发表期刊	CARCINOGENESIS 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	C-SRC ; V-SRC ; PROTEIN ; AKT ; INFECTION ; ONCOGENE ; KINASE ; CONSERVATION ; ACTIVATION ; INHIBITORS
摘要	Human papillomavirus (HPV) E7 oncogene plays the most important role in cervical cancer. However, whether E7 oncoprotein is continuously expressed, associated with AKT((Ser473))/p-Src((Tyr527)) signaling to trigger cervical carcinogenesis remains unclear. Here, we explored first if HPV16 E7 oncoprotein could be detected in clinical biopsies and is sustainedly expressed, and then investigated how this oncoprotein interacted with AKT((Ser473))/p-Src((Tyr527)) signaling in cancer progression. We used Z(HPV16E7)384 affibody to detect E7 expression in HPV16-positive cervical cancer biopsies and animal tumors by immunohistochemistry (IHC). Results showed that Z(HPV16E7)384 affibody had intense and specific staining for E7 oncoprotein in the detected specimen. The E7 oncoprotein was continuously expressed to correspond with the development of precancerous lesions to invasive cervical cancer. IHC staining also revealed that AKT, p-AKT((Ser473)), Src and p-Src((Tyr527)) proteins were expressed in both patient biopsies and animal tumors, with the highest levels of p-AKT((Ser473))/p-Src((Tyr527)) present in invasive cancer. Furthermore, siRNA experiments revealed that HPV16 E7 knockdown significantly impaired expression of p-AKT((Ser473))/p-Src((Tyr527)) in both HPV16 E7-positive cancer cells and transformed cells. In addition, transient expression of HPV16 E7 protein promoted significantly expression of p-AKT((Ser473)/)p-Src((Tyr527)) in primary human keratinocytes. Finally, co-immunoprecipitation analysis proved that HPV 16 E7 protein interacted reciprocally with p-AKT((Ser473))/p-Src((Tyr527)). In conclusion, we demonstrate that HPV16 E7 oncoprotein is continuously expressed to promote expression of p-AKT((Ser473))/p-Src((Tyr527)) leading to drive the initiation and progression of cervical cancer. Our data provide a novel insight that HPV16 E7 activates p-AKT((Ser473))/p-Src((Tyr527)) to establish a mechanistic link between the oncogene and the AKT/Src signaling to trigger cervical carcinogenesis.
资助项目	National Nature Science Foundation of China [81772791, 81172463]
出版者	OXFORD UNIV PRESS
出版地	OXFORD
ISSN	0143-3334
EISSN	1460-2180
卷号	43 期号:5 页码:479-493
DOI	10.1093/carcin/bgac010
页数	15
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000770423700001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	35134836
SCOPUSEID	2-s2.0-85128181000
通讯作者地址	[Zhu, Xueqiong]Department of Obstetrics and Gynaecology,Second Affiliated Hospital,Yuyin Children Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Cancer Research
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/148666
专题	附属第一医院基础医学院（机能实验教学中心）附属第二医院基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者	Zhu, Xueqiong
作者单位	1.Department of Pathology,First Affiliated Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Department of Obstetrics and Gynaecology,Second Affiliated Hospital,Yuyin Children Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.School of Basic Medical Science,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 4.Diamantina Institute for Cancer Immunology and Metabolic Medicine,University of Queensland,TRI,Woolloongabba,4102,Australia; 5.Australian Institute for Bioengineering and Nanotechnology,University of Queensland,St Lucia,4067,Australia; 6.Institute of Molecular Virology and Immunology,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
第一作者单位	附属第一医院
通讯作者单位	附属第二医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Lin, Zhongmin,Zhao, Yu,Li, Qijia,et al. Sustained expression of HPV16 E7 oncoprotein promotes p-AKT((Ser473))/p-Src((Tyr527)) signaling to drive precancerous lesions to invasive cervical cancer[J]. CARCINOGENESIS,2022,43(5):479-493.
APA	Lin, Zhongmin., Zhao, Yu., Li, Qijia., Ci, Xingyuan., Ye, Xiaoxian., ... & Zhao, Kong-Nan. (2022). Sustained expression of HPV16 E7 oncoprotein promotes p-AKT((Ser473))/p-Src((Tyr527)) signaling to drive precancerous lesions to invasive cervical cancer. CARCINOGENESIS, 43(5), 479-493.
MLA	Lin, Zhongmin,et al."Sustained expression of HPV16 E7 oncoprotein promotes p-AKT((Ser473))/p-Src((Tyr527)) signaling to drive precancerous lesions to invasive cervical cancer".CARCINOGENESIS 43.5(2022):479-493.