SMAD4 and metastatic neoplasm: Next, we silenced HMGA1 via lentiviral delivery of short hairpin RNAs (shRNAs) targeting 2 different sequences (49) in cell lines from primary and metastatic tumors harboring common PDAC mutations: (a) E3LZ10.7 (66), from a liver metastasis with KRASG12D and homozygous SMAD4 deletion; (b) MIA PaCa-2 (67), from a primary PDAC with homozygous CDKN2A/p16INK4A deletion, mutant KRASG12C, and TP53; and (c) AsPC-1 (67), from PDAC ascites fluid with homozygous mutations in KRASG12D, TP53C135fs*35, and CDKN2AL78fs*41.