Afterwards, start a series of proteolytic cascade reactions to break down the extracellular matrix’s components and encourage tumor invasion and metastasis.142,151 Additionally, the uPA-uPAR connection triggers signals that promote tumor-promoting gene expression and cell survival and proliferation.152 Unlike normal tissues, uPA and uPAR levels are constitutively increased in majority of cancer types.153,154 thus, uPA and uPAR are often considered as attractive enzyme stimulation response target for smart nanoparticles. The gene discussed is PLAU; the disease is cancer.