Further functional validation and mechanistic studies revealed that ICAM3 is highly expressed in various types of cancers, such as breast cancer and lung cancer, compared to normal tissues and that ICAM3 activates Src through the intracellular segment YLPL sequence recruitment, which in turn activates the PI3K/AKT signaling pathway, enhancing the activity of the stemness molecule OCT4 and mediating cancer stemness. Here, AKT1 is linked to lung cancer.