5q22.2

Sporadic colorectal cancer

Mouse experiments have shown that MCC is a tumour suppressor gene in colorectal cancer (Starr et al., 2009). In vitro experiments indicate that loss of MCC expression can impact on multiple signalling pathways but most strikingly on the activation of β-catenin directed transcription (Fukuyama et al., 2008). Aberrant activation of Wnt signalling is widely accepted as a major event in colorectal carcinogenesis and is mostly caused by APC mutations. It has been suggested that MCC silencing is also important in activating β-catenin, particularly in the context of the serrated neoplasia pathway where APC mutations are less common but MCC methylation is frequent (Kohonen-Corish et al., 2007; Fukuyama et al., 2008; Li et al., 2013). Other possible tumour promoting mechanisms of MCC silencing include impaired DNA damage response to single-strand DNA breaks (Pangon et al., 2010). Site-specific phosphorylation of MCC regulates G2/M cell cycle arrest and loss of MCC is thus expected to promote proliferation of damaged cells. MCC also regulates lamellipodia formation in epithelial cells which suggests that MCC silencing could affect epithelial restitution in the colon (Pangon et al., 2012).

Hepatocellular carcinoma

Loss of MCC expression in hepatocellular carcinoma is associated with aberrant activation of β-catenin (Shukla et al., 2013). MCC knockdown in vitro causes increased proliferation of hepatocellular cancer cells and is accompanied by increased G1/S transition (Lim et al., 2013).

Loss of MCC expression has been studied in relation to chemotherapy responsiveness in acute myeloid leukemia. Lack of induction of MCC expression is associated with poorer responsiveness to cytarabine (Gamazon et al., 2013).