SMAD4 and neoplasm: Activation of oncogenic KRAS (38) or inactivation of tumor suppressor TP53 (39), SMAD4 (40) or CDKN2A (41), Krüppel-like Factor 5 (KLF5), is increased in PDAC which promotes proliferation and also acinar-to-ductal metaplasia, PanIN, and leads to tumor growth in mice (42).