Invasive cells at the tumor front express L1 (brown).
Colon cancer cells grown at low but not high densities express high levels of L1. Because 90% of colon cancer cells have aberrant β-catenin signaling, the team tested the response of L1 promoter constructs to β-catenin siRNA and dominant-negative TCF proteins and found that the β-catenin/TCF complex activates the L1 gene. Furthermore, L1 expression increased cell motility and matrix invasion in fibroblasts and colon cancer cells. In patient samples, L1 was expressed only at the invading margins of tumors, not in the cell-dense center.
L1 expression in both cell culture and patient samples was accompanied by expression of ADAM10, a metalloproteinase known to clip the extracellular domain of L1. The team is currently investigating whether ADAM10 is also directly regulated by β-catenin/TCF, and how L1 confers the invasive properties on tumor cells.