CD44 and cancer: Zou et al. (2011) have reported that SPP1 interacts with ITGB1 increase mesenchymal stem cells (MSCs) motility resulting in the enhanced metastasis and migration of cancer cells (Orian-Rousseau, 2010). In NSCLC, SPP1 induces vascular endothelial growth factor (VEGF) expression while facilitating disease progression (Lin et al., 2015). In colorectal cell, SPP1 negatively regulates T cell activation by bonding to CD44 and promote cancer progression (Shurin, 2018; Supplementary Figure S2A).