Human papillomavirus type 16 E5 oncoprotein as a new target for cervical cancer treatment.
Human papillomavirus (HPV) infection is considered to be the necessary cause of cervical cancer. E6 and E7 oncoproteins of HPV have been known to play major roles in malignant transformation of cervical cells, inhibiting the tumor suppressors p53 and Rb. However, the role of E5 oncoprotein has been relatively less defined. HPV 16 E5 is a hydrophobic membrane-bound protein which associates with the Golgi apparatus, endoplasmic reticulum and perinuclear membrane. Accumulating evidences have suggested that E5 oncoprotein may also contribute to cervical carcinogenesis through modulating cellular signaling pathways in addition to augmenting the immortalization potential of E6 and E7. Multiple mechanisms, including activation of EGFR or inflammatory cell signaling pathway, have been implicated in malignant transformation by HPV 16 E5. Therefore, targeting E5 may be a rational approach for chemoprevention and treatment of cervical cancer, and understanding its oncogenic processes may help us to design novel therapeutic strategies. In this review, we discussed the roles of HPV 16 E5 in cervical carcinogenesis, altering several cellular signaling pathways involved in cell proliferation, angiogenesis and apoptosis.
Kim
Mi-Kyung
MK
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kim
Hee Seung
HS
Kim
Su-Hyeong
SH
Oh
Jung-Min
JM
Han
Jae Yong
JY
Lim
Jeong Mook
JM
Juhnn
Yong-Sung
YS
Song
Yong-Sang
YS
D000818:Animals; D017209:Apoptosis; D019496:Cancer Vaccines / Q000627:therapeutic use; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000086082:Viroporin Proteins
D019496:Cancer Vaccines; D066246:ErbB Receptors; D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins