AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas

Abstract The progression of colorectal cancer (CRC) has been well studied and understood with the development of molecular and genetic techniques. However, specific marker(s) that could be used to predict lymph node (LN) involvement, which is the most important prognostic factor for CRC, have not be...

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Autores principales:	Dasom Kim, Ji Wook Moon, Dong Hwa Min, Eun Sun Ko, Bokyung Ahn, Eun Sun Kim, Ji-Yun Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31eaedf5438743e889552c6971675cae
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spelling	oai:doaj.org-article:31eaedf5438743e889552c6971675cae2021-12-02T19:16:14ZAHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas10.1038/s41598-021-99375-w2045-2322https://doaj.org/article/31eaedf5438743e889552c6971675cae2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99375-whttps://doaj.org/toc/2045-2322Abstract The progression of colorectal cancer (CRC) has been well studied and understood with the development of molecular and genetic techniques. However, specific marker(s) that could be used to predict lymph node (LN) involvement, which is the most important prognostic factor for CRC, have not been identified so far. Our previous study, in which network analysis of LN(+) and LN(−) CRC gene expression was carried out with data obtained from the Cancer Genome Atlas, led to the identification of AHA1. AHA1 is a co-chaperone activator of the Hsp90 ATPase activity. However, the role of AHA1 expression in cancer cells is still unclear. To investigate how AHA1 expression regulates the cancer cell progression and/or metastasis of human CRC, the expression levels of AHA1 and Hsp90 were examined in 105 CRC tissue samples and compared with those in paired normal tissue. The RNA expression levels of AHA1 and Hsp90aa1, but not Hsp90ab, were significantly higher in cancer tissues than in adjacent paired normal tissues (p = 0.032 and p = 0.0002, respectively). In particular, AHA1, but not Hsp90aa1 and Hsp90ab, was closely associated with the TNM stage, LN stage, and tumor metastasis (p = 0.035, p = 0.012, and p = 0.0003, respectively). Moreover, the expression of AHA1 was not only higher in the CRC cell lines than in the normal colon fibroblast cell line but was also associated with the progression of these CRC cell lines. Overexpression of AHA1 in SW480 cells increased, whereas suppression of AHA1 expression in HCT116 cells reduced cell migration and invasion through the regulation of Snail, E-cadherin, pSRC, and pAKT, which are associated with EMT signaling. Taken together, our study suggests that AHA1 contributes to the metastatic advantage of human CRC.Dasom KimJi Wook MoonDong Hwa MinEun Sun KoBokyung AhnEun Sun KimJi-Yun LeeNature 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 Dasom Kim Ji Wook Moon Dong Hwa Min Eun Sun Ko Bokyung Ahn Eun Sun Kim Ji-Yun Lee AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas
description	Abstract The progression of colorectal cancer (CRC) has been well studied and understood with the development of molecular and genetic techniques. However, specific marker(s) that could be used to predict lymph node (LN) involvement, which is the most important prognostic factor for CRC, have not been identified so far. Our previous study, in which network analysis of LN(+) and LN(−) CRC gene expression was carried out with data obtained from the Cancer Genome Atlas, led to the identification of AHA1. AHA1 is a co-chaperone activator of the Hsp90 ATPase activity. However, the role of AHA1 expression in cancer cells is still unclear. To investigate how AHA1 expression regulates the cancer cell progression and/or metastasis of human CRC, the expression levels of AHA1 and Hsp90 were examined in 105 CRC tissue samples and compared with those in paired normal tissue. The RNA expression levels of AHA1 and Hsp90aa1, but not Hsp90ab, were significantly higher in cancer tissues than in adjacent paired normal tissues (p = 0.032 and p = 0.0002, respectively). In particular, AHA1, but not Hsp90aa1 and Hsp90ab, was closely associated with the TNM stage, LN stage, and tumor metastasis (p = 0.035, p = 0.012, and p = 0.0003, respectively). Moreover, the expression of AHA1 was not only higher in the CRC cell lines than in the normal colon fibroblast cell line but was also associated with the progression of these CRC cell lines. Overexpression of AHA1 in SW480 cells increased, whereas suppression of AHA1 expression in HCT116 cells reduced cell migration and invasion through the regulation of Snail, E-cadherin, pSRC, and pAKT, which are associated with EMT signaling. Taken together, our study suggests that AHA1 contributes to the metastatic advantage of human CRC.
format	article
author	Dasom Kim Ji Wook Moon Dong Hwa Min Eun Sun Ko Bokyung Ahn Eun Sun Kim Ji-Yun Lee
author_facet	Dasom Kim Ji Wook Moon Dong Hwa Min Eun Sun Ko Bokyung Ahn Eun Sun Kim Ji-Yun Lee
author_sort	Dasom Kim
title	AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas
title_short	AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas
title_full	AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas
title_fullStr	AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas
title_full_unstemmed	AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas
title_sort	aha1 regulates cell migration and invasion via the emt pathway in colorectal adenocarcinomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/31eaedf5438743e889552c6971675cae
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AHA1 regulates cell migration and invasion via the EMT pathway in colorectal adenocarcinomas

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