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However, the expression and function of ITLN1 in colorectal cancer (CRC) remain unknown. To identify novel prognostic markers or therapeutic targets for CRC, we focused on ITLN1 protein. By immunohistochemistry, 87 (59%) of 148 CRC cases showed reduced expression of ITLN1. ITLN1\u2010reduced CRC cases were associated with higher M grades (<jats:italic>P<\/jats:italic> = 0.0017) than ITLN1\u2010retained CRC cases. Furthermore, the cases with ITLN1 retained expression tended toward a more favorable prognosis than those with reduced expression. Cell growth of the CRC cell lines transfected with ITLN1 siRNA were greater than those of the negative control cell lines transfected with siRNA. Levels of phosphorylated epidermal growth factor receptor, Erk and Akt were higher in the CRC cells transfected with ITLN1 siRNA than in control cells. Immunohistochemical analysis of human colorectal polyp specimens also revealed a sequential decrease in the expression of ITLN1 through both the conventional adenoma\u2013carcinoma pathway and the serrated pathway. 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