NNK activates ERK1 and ERK2 through α7nAChR/Ca2+ Influx/PKC/Raf/MAPK/ERK kinase (MEK) to phosphorylate μ-calpain and m-calpain, leading to calpain activation and secretion and promoting the migration and spread of cancer cells in vivo. The gene discussed is CAPN2; the disease is cancer.