Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer

Abstract Ovarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ho-Jun Shih, Hsin-Fang Chang, Chi-Ling Chen, Pao-Ling Torng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/567b054f6cf249bdba035fe8ce095779
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:567b054f6cf249bdba035fe8ce095779
record_format	dspace
spelling	oai:doaj.org-article:567b054f6cf249bdba035fe8ce0957792021-11-28T12:16:50ZDifferential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer10.1038/s41598-021-02400-12045-2322https://doaj.org/article/567b054f6cf249bdba035fe8ce0957792021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02400-1https://doaj.org/toc/2045-2322Abstract Ovarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously identified as a growth/invasion/metastasis suppressor of ovarian cancer, plays a key role in inhibiting tumor angiogenesis. Although IGFBP3 can effectively downregulate tumor proliferation and vasculogenesis, its effects are only transient. Tumors enter a hypoxic state when they grow large and without blood vessels; then, the tumor cells activate HIFs to regulate cell metabolism, proliferation, and induce vasculogenesis to adapt to hypoxic stress. After IGFBP3 was transiently expressed in highly invasive ovarian cancer cell line and heterotransplant on mice, the xenograft tumors demonstrated a transient growth arrest with de-vascularization, causing tumor cell hypoxia. Tumor re-proliferation was associated with early HIF-1α and later HIF-2α activations. Both HIF-1α and HIF-2α were related to IGFBP3 expressions. In the down-expression of IGFBP3 in xenograft tumors and transfectants, HIF-2α was the major activated protein. This study suggests that HIF-2α presentation is crucial in the switching of epithelial ovarian cancer from dormancy to proliferation states. In highly invasive cells, the cancer hallmarks associated with aggressiveness could be activated to escape from the growth restriction state.Ho-Jun ShihHsin-Fang ChangChi-Ling ChenPao-Ling TorngNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ho-Jun Shih Hsin-Fang Chang Chi-Ling Chen Pao-Ling Torng Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
description	Abstract Ovarian cancer is the most lethal gynecological cancer, and it is frequently diagnosed at advanced stages, with recurrences after treatments. Treatment failure and resistance are due to hypoxia-inducible factors (HIFs) activated by cancer cells adapt to hypoxia. IGFBP3, which was previously identified as a growth/invasion/metastasis suppressor of ovarian cancer, plays a key role in inhibiting tumor angiogenesis. Although IGFBP3 can effectively downregulate tumor proliferation and vasculogenesis, its effects are only transient. Tumors enter a hypoxic state when they grow large and without blood vessels; then, the tumor cells activate HIFs to regulate cell metabolism, proliferation, and induce vasculogenesis to adapt to hypoxic stress. After IGFBP3 was transiently expressed in highly invasive ovarian cancer cell line and heterotransplant on mice, the xenograft tumors demonstrated a transient growth arrest with de-vascularization, causing tumor cell hypoxia. Tumor re-proliferation was associated with early HIF-1α and later HIF-2α activations. Both HIF-1α and HIF-2α were related to IGFBP3 expressions. In the down-expression of IGFBP3 in xenograft tumors and transfectants, HIF-2α was the major activated protein. This study suggests that HIF-2α presentation is crucial in the switching of epithelial ovarian cancer from dormancy to proliferation states. In highly invasive cells, the cancer hallmarks associated with aggressiveness could be activated to escape from the growth restriction state.
format	article
author	Ho-Jun Shih Hsin-Fang Chang Chi-Ling Chen Pao-Ling Torng
author_facet	Ho-Jun Shih Hsin-Fang Chang Chi-Ling Chen Pao-Ling Torng
author_sort	Ho-Jun Shih
title	Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
title_short	Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
title_full	Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
title_fullStr	Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
title_full_unstemmed	Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
title_sort	differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/567b054f6cf249bdba035fe8ce095779
work_keys_str_mv	AT hojunshih differentialexpressionofhypoxiainduciblefactorsrelatedtotheinvasivenessofepithelialovariancancer AT hsinfangchang differentialexpressionofhypoxiainduciblefactorsrelatedtotheinvasivenessofepithelialovariancancer AT chilingchen differentialexpressionofhypoxiainduciblefactorsrelatedtotheinvasivenessofepithelialovariancancer AT paolingtorng differentialexpressionofhypoxiainduciblefactorsrelatedtotheinvasivenessofepithelialovariancancer
_version_	1718408077682671616

Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer

Ejemplares similares