This is consistent with the finding that FHL2 promotes invasive p

This is consistent with the finding that FHL2 promotes invasive potential in colon cancer (Zhang et al, 2010). During cancer progression, advanced tumour cells frequently exhibit a conspicuous downregulation of epithelial markers and a loss of intercellular junctions, resulting in a loss of epithelial selleck chemicals CHIR99021 polarity and reduced intercellular adhesion. These alterations are often accompanied by nuclear accumulation of ��-catenin, increased cell motility and expression of mesenchymal-specific proteins such as vimentin (Vermeulen et al, 1995; Huber et al, 2005; Turley et al, 2008; Iwatsuki et al, 2010). This process called EMT can therefore promote invasion and metastasis (Bates and Mercurio, 2005; Huber et al, 2005; Turley et al, 2008). One of the decreased epithelial markers during EMT is E-cadherin (De Wever et al, 2008).

Four-and-a-half LIM domains protein 2 negatively regulates the transcription of E-cadherin through interaction with Snail 1 (Zhang et al, 2010, 2011). Moreover, FHL2 stimulates vimentin and matrix metalloproteinase-9 expressions (Zhang et al, 2010). Other arguments for a role of FHL2 in EMT come from a gain-of-function experiment in which the overexpression of FHL2 in a fish pre-osteoblastic cell line promoted cell dedifferentiation and altered gene expression profile in agreement with an EMT-like phenotype (Rafael et al, 2012). In contrast to others (Zhang et al, 2010), we did not detect nuclear FHL2 expression in CRC, using a well-defined and validated antibody; therefore, we suggest that FHL2 interacts via cytoplasmic/cell periphery protein interactions, rather than via direct transcriptional activation or repression, in the progression of CRC, including EMT.

Multiple functions have been ascribed to FHL2, and it is puzzling how a protein that consists of LIM domains only and that lacks any obvious enzymatic activity can exert such a functional diversity. Four-and-a-half LIM domains protein 2 can interact with >50 different proteins that belong to different functional classes, including receptors (Kurakula et al, 2011; Matulis and Mayo, 2012), structural proteins (Lange et al, 2002; Coghill et al, 2003), transcription factors and cofactors (Samson et al, 2004; Han et al, 2009; Hubbi et al, 2012), splicing factors (Dye and Patton, 2001; Ng et al, 2002), DNA replication and repair enzymes (Chan et al, 2000; Yan et al, 2003), and enzymes (Jiang et al, 2002; Lange et al, 2002; Wang et al, 2012).

The biological importance of many of these protein�Cprotein interactions has not been determined, but such information will contribute to further clarifying the roles of FHL2 in colorectal and other cancers. Cell-specific expression and cell-specific subcellular distribution of AV-951 FHL2, as well as the available concentrations of the interacting partners may partially favour certain interactions.

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