Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer

Abstract Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-medi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Eun-Hee Lee, Kon-Young Ji, Eun-Mi Kim, Su-Man Kim, Hyeong-Woo Song, Ha-Rim Choi, Byung Yeoup Chung, Hyo Jin Choi, Hyoung-Woo Bai, Hyung-Sik Kang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6dcd0e8672234eb1897baec83bcb2898
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6dcd0e8672234eb1897baec83bcb2898
record_format	dspace
spelling	oai:doaj.org-article:6dcd0e8672234eb1897baec83bcb28982021-12-02T12:32:20ZBlockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer10.1038/s41598-017-05977-82045-2322https://doaj.org/article/6dcd0e8672234eb1897baec83bcb28982017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05977-8https://doaj.org/toc/2045-2322Abstract Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells. Moreover, myeloid zinc finger protein 1 (MZF1) binds directly to the Axl promoter in HE6F cells. Axl expression was regulated by HPV16E6-mediated PTEN/AKT signalling pathway, and Axl promoter activity was regulated through MZF1 activation in cervical cancer, which promoted malignancy. Axl silencing suppressed the metastasis of Caski cells and enhanced the susceptibility to NK cell-mediated killing of HE6F cells. In addition, the expression of Axl and MZF1 was highly correlated with clinical stage of cervical cancer and HPV16/18 infection. Taken together, Axl expression was induced by HPV16E6 in cervical cancer cells, suggesting that blockade of Axl signalling might be an effective way to reduce the progression of cervical cancer.Eun-Hee LeeKon-Young JiEun-Mi KimSu-Man KimHyeong-Woo SongHa-Rim ChoiByung Yeoup ChungHyo Jin ChoiHyoung-Woo BaiHyung-Sik KangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eun-Hee Lee Kon-Young Ji Eun-Mi Kim Su-Man Kim Hyeong-Woo Song Ha-Rim Choi Byung Yeoup Chung Hyo Jin Choi Hyoung-Woo Bai Hyung-Sik Kang Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
description	Abstract Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells. Moreover, myeloid zinc finger protein 1 (MZF1) binds directly to the Axl promoter in HE6F cells. Axl expression was regulated by HPV16E6-mediated PTEN/AKT signalling pathway, and Axl promoter activity was regulated through MZF1 activation in cervical cancer, which promoted malignancy. Axl silencing suppressed the metastasis of Caski cells and enhanced the susceptibility to NK cell-mediated killing of HE6F cells. In addition, the expression of Axl and MZF1 was highly correlated with clinical stage of cervical cancer and HPV16/18 infection. Taken together, Axl expression was induced by HPV16E6 in cervical cancer cells, suggesting that blockade of Axl signalling might be an effective way to reduce the progression of cervical cancer.
format	article
author	Eun-Hee Lee Kon-Young Ji Eun-Mi Kim Su-Man Kim Hyeong-Woo Song Ha-Rim Choi Byung Yeoup Chung Hyo Jin Choi Hyoung-Woo Bai Hyung-Sik Kang
author_facet	Eun-Hee Lee Kon-Young Ji Eun-Mi Kim Su-Man Kim Hyeong-Woo Song Ha-Rim Choi Byung Yeoup Chung Hyo Jin Choi Hyoung-Woo Bai Hyung-Sik Kang
author_sort	Eun-Hee Lee
title	Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
title_short	Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
title_full	Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
title_fullStr	Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
title_full_unstemmed	Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer
title_sort	blockade of axl signaling ameliorates hpv16e6-mediated tumorigenecity of cervical cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6dcd0e8672234eb1897baec83bcb2898
work_keys_str_mv	AT eunheelee blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT konyoungji blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT eunmikim blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT sumankim blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT hyeongwoosong blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT harimchoi blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT byungyeoupchung blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT hyojinchoi blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT hyoungwoobai blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer AT hyungsikkang blockadeofaxlsignalingameliorateshpv16e6mediatedtumorigenecityofcervicalcancer
_version_	1718394099689586688

Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer

Ejemplares similares