Wnt5a produced by mammary luminal cells acts in a paracrine fashion, through binding to Ryk receptor on basal tumor initiating cells (TICs) and forms a complex with transforming growth factor β receptor 1 (TGFβR1), leading to the phosphorylation and activation of SMAD2, a signaling protein involved in regulating cell differentiation, and suppression of basal cells growth and tumor initiation [46]. Here, SMAD2 is linked to neoplasm.