Open AccessVimentin, colon cancer progression and resistance to butyrate and other HDAC is
Author(s) -
Lazarova Darina L.,
Bordonaro Michael
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12850
Subject(s) - butyrate , vimentin , cancer research , wnt signaling pathway , biology , histone deacetylase , histone deacetylase inhibitor , colorectal cancer , microbiology and biotechnology , cancer , immunology , histone , signal transduction , gene , immunohistochemistry , biochemistry , genetics , fermentation
Dietary fibre protects against colorectal cancer ( CRC ) most likely through the activity of its fermentation product, butyrate. Butyrate functions as a histone deacetylase inhibitor ( HDAC i) that hyperactivates Wnt signalling and induces apoptosis of CRC cells. However, individuals who consume a high‐fibre diet may still develop CRC ; therefore, butyrate resistance may develop over time. Furthermore, CRC cells that are resistant to butyrate are cross‐resistant to clinically relevant therapeutic HDAC is, suggesting that the development of butyrate resistance in vivo can result in HDAC i‐resistant CRC s. Butyrate/ HDAC i‐resistant CRC cells differ from their butyrate/ HDAC i‐sensitive counterparts in the expression of many genes, including the gene encoding vimentin ( VIM ) that is usually expressed in normal mesenchymal cells and is involved in cancer metastasis. Interestingly, vimentin is overexpressed in butyrate/ HDAC i‐resistant CRC cells although Wnt signalling is suppressed in such cells and that VIM is a Wnt activity‐targeted gene. The expression of vimentin in colonic neoplastic cells could be correlated with the stage of neoplastic progression. For example, comparative analyses of LT 97 microadenoma cells and SW 620 colon carcinoma cells revealed that although vimentin is not detectable in LT 97 cells, it is highly expressed in SW 620 cells. Based upon these observations, we propose that the differential expression of vimentin contributes to the phenotypic differences between butyrate‐resistant and butyrate‐sensitive CRC cells, as well as to the differences between early‐stage and metastatic colorectal neoplastic cells. We discuss the hypothesis that vimentin is a key factor integrating epithelial to mesenchymal transition, colonic neoplastic progression and resistance to HDAC is.