In:
Cancer Science, Wiley, Vol. 109, No. 8 ( 2018-08), p. 2520-2531
Abstract:
Current therapies for pancreatic ductal cancer ( PDAC ) do not sufficiently control distant metastasis. Thus, new therapeutic targets are urgently needed. Numerous studies have suggested that the epithelial‐mesenchymal transition ( EMT ) is pivotal for metastasis of carcinomas. The fact that the EMT is reversible suggests the possibility that it is induced by an epigenetic mechanism. In this study, we aimed to investigate the role of histone deacetylase 1 ( HDAC 1), which is an epigenetic mechanism on distant metastasis of PDAC . We investigated the HDAC 1 expression in 103 resected PDAC specimens obtained from patients who were treated with/without preoperative therapy using immunohistochemistry. To validate the findings in the clinical samples, we evaluated the HDAC 1 activity, the EMT ‐associated genes and the migration/invasion ability in vitro, and performed an HDAC 1 inhibitor assay. The high expression of HDAC 1 in clinical samples was significantly associated with poor progression‐free survival, especially distant metastasis‐free survival. In vitro, HDAC 1 inhibitors decreased the invasion ability and reversed the EMT change; the only factor to show a concomitant decrease was the expression of SNAIL . We confirmed that the HDAC 1 expression was associated with the SNAIL expression in clinical samples. Moreover, the resistant cells and parental cells did not show any significant differences in the expression of HDAC 1; this was consistent with the finding that preoperative therapy did not alter the HDAC 1 expression in clinical samples. The targeting of HDAC 1, which could suppress metastasis by inhibiting the EMT , is a promising treatment option for PDAC .
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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