Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer

The presence of an activating mutation of the Wnt/β-catenin signaling pathway is found in ~90% of colorectal cancer (CRC) cases. Death domain-associated protein (DAXX), a nuclear protein, interacts with β-catenin in CRC cells. We investigated DAXX expression in 106 matched sample p...

Full description

Bibliographic Details
Main Authors: Ya-Chun Chen, Tsung-Hsien Lee, Shu-Ling Tzeng
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/10/1242
_version_ 1797710528607420416
author Ya-Chun Chen
Tsung-Hsien Lee
Shu-Ling Tzeng
author_facet Ya-Chun Chen
Tsung-Hsien Lee
Shu-Ling Tzeng
author_sort Ya-Chun Chen
collection DOAJ
description The presence of an activating mutation of the Wnt/&#946;-catenin signaling pathway is found in ~90% of colorectal cancer (CRC) cases. Death domain-associated protein (DAXX), a nuclear protein, interacts with &#946;-catenin in CRC cells. We investigated DAXX expression in 106 matched sample pairs of CRC and adjacent normal tissue by Western blotting. This study evaluated DAXX expression and its clinical implications in CRC. The results revealed that DAXX expression was significantly lower in the patients with the positive serum carcinoembryonic antigen (CEA) screening results compared to the patients with negative CEA screening levels (<i>p</i> &lt; 0.001). It has been reported that CD24 is a Wnt target in CRC cells. Here, we further revealed that DAXX expression was significantly correlated with CD24 expression (rho = 0.360, <i>p</i> &lt; 0.001) in 106 patients. Consistent with this, in the CEA-positive subgroup, of which the carcinomas expressed DAXX at low levels, they were significantly correlated with CD24 expression (rho = 0.461, <i>p</i> &lt; 0.005). Therefore, reduced DAXX expression is associated with reduced CD24 expression in CRC. Notably, in the Hct116 cells, DAXX knockdown using short-hairpin RNA against DAXX (shDAXX) not only caused significant cell proliferation, but also promoted metastasis. The DAXX-knockdown cells also demonstrated significantly decreased CD24 expression, however the intracellular localization of CD24 did not change. Thus, DAXX might be considered as a potential regulator of CD24 or &#946;-catenin expression, which might be correlated with proliferative and metastatic potential of CRC.
first_indexed 2024-03-12T06:52:41Z
format Article
id doaj.art-c8f3a575fe12424bb84086bd230c8b61
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-12T06:52:41Z
publishDate 2019-10-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-c8f3a575fe12424bb84086bd230c8b612023-09-03T00:11:17ZengMDPI AGCells2073-44092019-10-01810124210.3390/cells8101242cells8101242Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal CancerYa-Chun Chen0Tsung-Hsien Lee1Shu-Ling Tzeng2Institute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanThe presence of an activating mutation of the Wnt/&#946;-catenin signaling pathway is found in ~90% of colorectal cancer (CRC) cases. Death domain-associated protein (DAXX), a nuclear protein, interacts with &#946;-catenin in CRC cells. We investigated DAXX expression in 106 matched sample pairs of CRC and adjacent normal tissue by Western blotting. This study evaluated DAXX expression and its clinical implications in CRC. The results revealed that DAXX expression was significantly lower in the patients with the positive serum carcinoembryonic antigen (CEA) screening results compared to the patients with negative CEA screening levels (<i>p</i> &lt; 0.001). It has been reported that CD24 is a Wnt target in CRC cells. Here, we further revealed that DAXX expression was significantly correlated with CD24 expression (rho = 0.360, <i>p</i> &lt; 0.001) in 106 patients. Consistent with this, in the CEA-positive subgroup, of which the carcinomas expressed DAXX at low levels, they were significantly correlated with CD24 expression (rho = 0.461, <i>p</i> &lt; 0.005). Therefore, reduced DAXX expression is associated with reduced CD24 expression in CRC. Notably, in the Hct116 cells, DAXX knockdown using short-hairpin RNA against DAXX (shDAXX) not only caused significant cell proliferation, but also promoted metastasis. The DAXX-knockdown cells also demonstrated significantly decreased CD24 expression, however the intracellular localization of CD24 did not change. Thus, DAXX might be considered as a potential regulator of CD24 or &#946;-catenin expression, which might be correlated with proliferative and metastatic potential of CRC.https://www.mdpi.com/2073-4409/8/10/1242colorectal cancerdaxxcd24carcinoembryonic antigenproliferationmetastasis
spellingShingle Ya-Chun Chen
Tsung-Hsien Lee
Shu-Ling Tzeng
Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer
Cells
colorectal cancer
daxx
cd24
carcinoembryonic antigen
proliferation
metastasis
title Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer
title_full Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer
title_fullStr Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer
title_full_unstemmed Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer
title_short Reduced DAXX Expression Is Associated with Reduced CD24 Expression in Colorectal Cancer
title_sort reduced daxx expression is associated with reduced cd24 expression in colorectal cancer
topic colorectal cancer
daxx
cd24
carcinoembryonic antigen
proliferation
metastasis
url https://www.mdpi.com/2073-4409/8/10/1242
work_keys_str_mv AT yachunchen reduceddaxxexpressionisassociatedwithreducedcd24expressionincolorectalcancer
AT tsunghsienlee reduceddaxxexpressionisassociatedwithreducedcd24expressionincolorectalcancer
AT shulingtzeng reduceddaxxexpressionisassociatedwithreducedcd24expressionincolorectalcancer