It has been shown that TβRI-ICD associates with p300 and activates genes involved with tumour invasion, such as MMP2 [12, 42]; here, we show by knockdown of APPL proteins that the nuclear TβRI-ICD-APPL protein complex regulates MMP2 and MMP9 expression, which could promote cancer cell invasion (Figure 5C, 5D). The gene discussed is APPL1; the disease is cancer.