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

Abstract

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 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 (p < 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, p < 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, p < 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 β-catenin expression, which might be correlated with proliferative and metastatic potential of CRC.

Dynamic Activity of Histone H3-Specific Chaperone Complexes in Oncogenesis

“…Similarly, a study lead by Tzeng et al. demonstrated that DAXX suppresses Tcf4 transcriptional activity and induces G1 arrest of colon cancer cells, functions as tumor suppressor ( 127 ), and the knockdown of DAXX caused significant cell proliferation and promote metastasis ( 126 ). In PanNETs, DAXX/H3.3 complex suppresses target genes including Stanniocalcin 2 (STC2) by promoting H3K9me3 ( 129 ), suggesting that DAXX acts as a tumor suppressor.…”

“…For example, DAXX is overexpressed in many types of cancer such as prostate cancer ( 118 , 120 , 130 ), ovarian cancer ( 121 , 122 ), gastric cancer ( 123 ), and gliomas ( 14 ). DAXX is downregulated in advanced gastric cancer ( 125 ) and human colon adenocarcinoma cells ( 126 , 127 ), lung cancer ( 128 ), and PanNETs ( 129 ). One study suggests that DAXX binds to anaphase promoting complex (APC) coactivators Cdc20 and Cdh1 to inhibit the degradation of APC, thereby promoting chromosome instability during prostate cancer development ( 118 ).…”

Histone Chaperones and Digestive Cancer: A Review of the Literature

“…Chen [ 67 ] demonstrated that decreasing DAXX expression in the nucleus inhibits proliferation, migration, and invasion of GC cells, while elevated DAXX expression in the cytoplasm promotes migration and invasion. Based on the reported literature [ 69 , 70 , 72 ], the function of DAXX in CRC also appears to be contradictory. Chen [ 69 ] discovered that DAXX is expressed at a low level in CRC tissues and inhibits proliferation and migration.…”

Regulation of Hedgehog Signaling by miRNAs and Nanoformulations: A Possible Therapeutic Solution for Colorectal Cancer

“…Considering its abundance in CRC tumorous stem cells it has been reported as putative marker for the detection of invasiveness and metastasis. Cluster differentiation 24 is an emerging biomarker for CRC ( 140 ). Overexpression of CD24 is affiliated with tumor differentiation, invasion metastasis ( 141 ).…”