Functional properties of a new Wnt11 isoform expressed in colon carcinoma cell line HT29

Colon carcinoma is a common type of neoplastic transformation. The mechanisms of its establishment and progression have been studied for several decades. Aberrant activation of canonical Wnt signaling is frequently observed in colon carcinoma cells. Moreover, expression of “noncanonical” Wnt ligands is also detected in this type of cancer. However, the role of noncanonical Wnt signaling in carcinogenesis and colorectal cancer (CRC) progression is still unclear. To study the characteristics of noncanonical Wnt signaling activation in CRC, expression of “noncanonical” ligand hWnt11 was examined in HT29 human colon carcinoma cells. For the first time it was shown that alternative splicing accompanies hWnt11 expression in CRC. A new hWnt11 isoform (hWnt11sp3) was identified. Unlike hWnt11, the isoform is not secreted and lacks the ability to inhibit canonical Wnt signaling. Different functional properties of the ligand hWnt11 and its isoform may reflect a special role of alternative splicing in carcinogenesis and tumor progression, since aberrant activity of canonical Wnt signaling is observed in many tumor cells. The existence of several Wnt isoforms and the difference in their functional properties should be taken into account when investigating the role of Wnt ligands.