Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterised by dense desmoplasia and hypoxic microenvironment. Our previous reports demonstrated that hyaluronan (HA), especially low-molecular-weight HA, provides a favourable microenvironment for PDAC progression. However, the effect of hypoxia...

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Autores principales:	Takuya Oba, Norihiro Sato, Yasuhiro Adachi, Takao Amaike, Yuzan Kudo, Atsuhiro Koga, Shiro Kohi, Keiji Hirata
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c62b840d2c5d416786398c12bdf8cdc5
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spelling	oai:doaj.org-article:c62b840d2c5d416786398c12bdf8cdc52021-12-02T17:25:33ZHypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer10.1038/s41598-021-97752-z2045-2322https://doaj.org/article/c62b840d2c5d416786398c12bdf8cdc52021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97752-zhttps://doaj.org/toc/2045-2322Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterised by dense desmoplasia and hypoxic microenvironment. Our previous reports demonstrated that hyaluronan (HA), especially low-molecular-weight HA, provides a favourable microenvironment for PDAC progression. However, the effect of hypoxia on HA metabolism remains unknown. Using quantitative real-time RT-PCR and western blot analysis, we analysed the changes in the expression of HA-synthesizing enzymes (HAS2 and HAS3) and HA-degrading enzymes (HYAL1, KIAA1199/CEMIP) in PDAC cell lines under hypoxic conditions. Hypoxia increased the mRNA and protein expression of KIAA1199, whereas it decreased HYAL1 expression. The expression of HAS3 was increased and HAS2 remained unchanged in response to hypoxia. The effect of KIAA1199 on hypoxia-induced cell migration was determined using a transwell migration assay and small-interfering RNA (siRNA). Hypoxia enhanced the migratory ability of PDAC cells, which was inhibited by KIAA1199 knockdown. We also used immunohistochemistry to analyse the protein expression of hypoxia inducible factor (HIF) 1α and KIAA1199 in PDAC tissues. There was a significant immunohistochemically positive correlation between KIAA1199 and HIF1α. These findings suggest that hypoxia-induced KIAA1199 expression may contribute to enhanced motility in PDAC.Takuya ObaNorihiro SatoYasuhiro AdachiTakao AmaikeYuzan KudoAtsuhiro KogaShiro KohiKeiji HirataNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuya Oba Norihiro Sato Yasuhiro Adachi Takao Amaike Yuzan Kudo Atsuhiro Koga Shiro Kohi Keiji Hirata Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer
description	Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterised by dense desmoplasia and hypoxic microenvironment. Our previous reports demonstrated that hyaluronan (HA), especially low-molecular-weight HA, provides a favourable microenvironment for PDAC progression. However, the effect of hypoxia on HA metabolism remains unknown. Using quantitative real-time RT-PCR and western blot analysis, we analysed the changes in the expression of HA-synthesizing enzymes (HAS2 and HAS3) and HA-degrading enzymes (HYAL1, KIAA1199/CEMIP) in PDAC cell lines under hypoxic conditions. Hypoxia increased the mRNA and protein expression of KIAA1199, whereas it decreased HYAL1 expression. The expression of HAS3 was increased and HAS2 remained unchanged in response to hypoxia. The effect of KIAA1199 on hypoxia-induced cell migration was determined using a transwell migration assay and small-interfering RNA (siRNA). Hypoxia enhanced the migratory ability of PDAC cells, which was inhibited by KIAA1199 knockdown. We also used immunohistochemistry to analyse the protein expression of hypoxia inducible factor (HIF) 1α and KIAA1199 in PDAC tissues. There was a significant immunohistochemically positive correlation between KIAA1199 and HIF1α. These findings suggest that hypoxia-induced KIAA1199 expression may contribute to enhanced motility in PDAC.
format	article
author	Takuya Oba Norihiro Sato Yasuhiro Adachi Takao Amaike Yuzan Kudo Atsuhiro Koga Shiro Kohi Keiji Hirata
author_facet	Takuya Oba Norihiro Sato Yasuhiro Adachi Takao Amaike Yuzan Kudo Atsuhiro Koga Shiro Kohi Keiji Hirata
author_sort	Takuya Oba
title	Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer
title_short	Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer
title_full	Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer
title_fullStr	Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer
title_full_unstemmed	Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer
title_sort	hypoxia increases kiaa1199/cemip expression and enhances cell migration in pancreatic cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c62b840d2c5d416786398c12bdf8cdc5
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Hypoxia increases KIAA1199/CEMIP expression and enhances cell migration in pancreatic cancer

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