In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5377-5377
Abstract:
Introduction & Methods: Gastric cancer represents one of the leading causes of cancer related death in the world second only to lung cancer resulting in 800,000 deaths per year. Aurora kinases, a family of serine/threonine kinases essential for cytokinesis and chromosome segregation, are frequently over-expressed in various cancer types. Moreover, Aurora kinase has recently been shown to directly regulate epigenetic changes (Guise et al., Mol Cell Proteomics. 2012 Nov;11(11):1220-9). Aurora kinase signaling may also impact E-cadherin function via a GSK3-α/β induced increase in β-catenin. E-cadherin deregulation has been implicated in gastric cancer, especially in diffuse types where it is mutated in many cases. We have profiled Aurora kinase signaling pathway activation and its effects on epigenetic and cytoskeletal changes in gastric cancer. Human gastric cancer tumor samples (n=10; 4 diffuse, 5 intestinal, 1 undifferentiated adenocardinoma) and patient matched normal mucosa were procured by laser capture microdissection. Reverse phase protein microarrays were used to quantify total and post-translationally modified proteins in cell signaling pathways directly and indirectly related to Aurora kinase. Results: We found a significant increase in histone deacetylase 4 levels (HDAC4, p & lt;0.0001) concomitant with increased phosphorylation of Aurora kinase (p & lt;0.1) and a decrease in phosphorylated GSK3-α/β (p & lt;0.05) in gastric tumor epithelia compared to patient matched normal mucosa. Gastric cancer samples of diffuse type showed a significantly reduced expression of E-Cadherin (p & lt;0.05) as compared to intestinal type gastric cancer. In contrast, patient samples with lymph node metastasis (n=6) were associated with an increased level of phospho-GSK3-α/β in both normal mucosa (p & lt;0.05) and matched tumor epithelia (p & lt;0.1). Conclusions: To our knowledge, this is the first time that increased levels of HDAC4 have been reported in gastric cancer. The demonstrated increase in Aurora kinase phosphorylation in gastric tumor epithelia may provide a mechanistic link to the observed HDAC4 upregulation. Citation Format: Lorenzo Colarossi, Lorenzo Memeo, Lance A. Liotta, Virginia Espina, Claudius Mueller. Profiling of aurora kinase signaling in microdissected gastric cancer samples indicates a significant increase in histone deacetylase 4 (HDAC4). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5377. doi:10.1158/1538-7445.AM2013-5377
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-5377
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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