Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.

Human Dachshund homologue 1 (DACH1) is a major component of the Retinal Determination Gene Network. Loss of DACH1 expression was found in breast, prostate, lung, endometrial, colorectal and hepatocellular carcinoma. To explore the expression, regulation and function of DACH1 in human esophageal canc...

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Autores principales:	Liang Wu, James G Herman, Malcolm V Brock, Kongming Wu, Gaoping Mao, Wenji Yan, Yan Nie, Hao Liang, Qimin Zhan, Wen Li, Mingzhou Guo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/643fbcbb5cc348b6a49dedbdb1c0608f
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spelling	oai:doaj.org-article:643fbcbb5cc348b6a49dedbdb1c0608f2021-11-18T08:22:34ZSilencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.1932-620310.1371/journal.pone.0095509https://doaj.org/article/643fbcbb5cc348b6a49dedbdb1c0608f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24743895/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Human Dachshund homologue 1 (DACH1) is a major component of the Retinal Determination Gene Network. Loss of DACH1 expression was found in breast, prostate, lung, endometrial, colorectal and hepatocellular carcinoma. To explore the expression, regulation and function of DACH1 in human esophageal cancer, 11 esophageal cancer cell lines, 10 cases of normal esophageal mucosa, 51 cases of different grades of dysplasia and 104 cases of primary esophageal squamous cancer were employed. Methylation specific PCR, immunohistochemistry, western blot, flow cytometry, small interfering RNAs, colony formation techniques and xenograft mice model were used. We found that DACH1 expression was regulated by promoter region hypermethylation in esophageal cancer cell lines. 18.8% (6 of 32) of grade 1, 42.1% (8 of 19) of grade 2 and grade 3 dysplasia (ED2,3), and 61.5% (64 of 104) of esophageal cancer were methylated, but no methylation was found in 10 cases of normal esophageal mucosa. The methylation was increased in progression tendency during esophageal carcinogenesis (P<0.01). DACH1 methylation was associated with poor differentiation (P<0.05) and late tumor stage (P<0.05). Restoration of DACH1 expression inhibited cell growth and activated TGF-β signaling in KYSE150 and KYSE510 cells. DACH1 suppressed human esophageal cancer cell tumor growth in xenograft mice. In conclusion, DACH1 is frequently methylated in human esophageal cancer and methylation of DACH1 is involved in the early stage of esophageal carcinogenesis. DACH1 expression is regulated by promoter region hypermethylation. DACH1 suppresses esophageal cancer growth by activating TGF-β signaling.Liang WuJames G HermanMalcolm V BrockKongming WuGaoping MaoWenji YanYan NieHao LiangQimin ZhanWen LiMingzhou GuoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e95509 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liang Wu James G Herman Malcolm V Brock Kongming Wu Gaoping Mao Wenji Yan Yan Nie Hao Liang Qimin Zhan Wen Li Mingzhou Guo Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.
description	Human Dachshund homologue 1 (DACH1) is a major component of the Retinal Determination Gene Network. Loss of DACH1 expression was found in breast, prostate, lung, endometrial, colorectal and hepatocellular carcinoma. To explore the expression, regulation and function of DACH1 in human esophageal cancer, 11 esophageal cancer cell lines, 10 cases of normal esophageal mucosa, 51 cases of different grades of dysplasia and 104 cases of primary esophageal squamous cancer were employed. Methylation specific PCR, immunohistochemistry, western blot, flow cytometry, small interfering RNAs, colony formation techniques and xenograft mice model were used. We found that DACH1 expression was regulated by promoter region hypermethylation in esophageal cancer cell lines. 18.8% (6 of 32) of grade 1, 42.1% (8 of 19) of grade 2 and grade 3 dysplasia (ED2,3), and 61.5% (64 of 104) of esophageal cancer were methylated, but no methylation was found in 10 cases of normal esophageal mucosa. The methylation was increased in progression tendency during esophageal carcinogenesis (P<0.01). DACH1 methylation was associated with poor differentiation (P<0.05) and late tumor stage (P<0.05). Restoration of DACH1 expression inhibited cell growth and activated TGF-β signaling in KYSE150 and KYSE510 cells. DACH1 suppressed human esophageal cancer cell tumor growth in xenograft mice. In conclusion, DACH1 is frequently methylated in human esophageal cancer and methylation of DACH1 is involved in the early stage of esophageal carcinogenesis. DACH1 expression is regulated by promoter region hypermethylation. DACH1 suppresses esophageal cancer growth by activating TGF-β signaling.
format	article
author	Liang Wu James G Herman Malcolm V Brock Kongming Wu Gaoping Mao Wenji Yan Yan Nie Hao Liang Qimin Zhan Wen Li Mingzhou Guo
author_facet	Liang Wu James G Herman Malcolm V Brock Kongming Wu Gaoping Mao Wenji Yan Yan Nie Hao Liang Qimin Zhan Wen Li Mingzhou Guo
author_sort	Liang Wu
title	Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.
title_short	Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.
title_full	Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.
title_fullStr	Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.
title_full_unstemmed	Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.
title_sort	silencing dach1 promotes esophageal cancer growth by inhibiting tgf-β signaling.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/643fbcbb5cc348b6a49dedbdb1c0608f
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Silencing DACH1 promotes esophageal cancer growth by inhibiting TGF-β signaling.

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