Reduced MAGI3 level by HPV18E6 contributes to Wnt/β‐catenin signaling activation and cervical cancer progression
Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ‐binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO‐1...
Saved in:
Published in | FEBS open bio Vol. 11; no. 11; pp. 3051 - 3062 |
---|---|
Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
John Wiley & Sons, Inc
01.11.2021
John Wiley and Sons Inc Wiley |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ‐binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO‐1 (PDZ) proteins. In this study, we demonstrated that the PDZ protein membrane‐associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) inhibited the Wnt/β‐catenin pathway, and subsequently cervical cancer (CC) cell migration and invasion, via decreasing β‐catenin levels. By reducing MAGI3 protein levels, HPV18 E6 promoted CC cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 was preferentially associated with the downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in CC. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in CC progression.
By reducing the level of MAGI3 protein, HPV18 E6 promotes cervical cancer cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 is preferentially associated with downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in cervical cancer. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in cervical cancer progression. |
---|---|
Bibliography: | Zhuoli Yang, Hua Liu and Ran Song contributed equally to this work ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-5463 2211-5463 |
DOI: | 10.1002/2211-5463.13298 |