The secreted mammalian Ly-6⁄urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is an endogenous ligand at the α7 subunit of the nicotinic acetylcholine receptor (nAChR). SLURP-1 has anti-tumourigenic properties. In the current study, we demonstrate that the challenge of HT-29 human colon cancer cells with nicotine for 24 h to increase cell growth via the α7nAChRs, caused a marked reduction of the protein expression of SLURP-1. We suggest that there is an interplay between acetylcholine and SLURP-1 in the HT-29 cells, both molecules serving as autocrine growth controlling ligands at the α7nAChR, where acetylcholine regulates the release of SLURP-1.