Yu-Kai Huang, Wei-Chung Cheng, Ting-Ting Kuo, Juan-Cheng Yang, Yang-Chang Wu, Heng-Hsiung Wu, Chia-Chien Lo, Chih-Ying Hsieh, Sze-Ching Wong, Chih-Hao Lu, Wan-Ling Wu, Shih-Jen Liu, Yi-Chuan Li, Ching-Chan Lin, Chia-Ning Shen, Mien-Chie Hung, Jaw-Town Lin, Chun-Chieh Yeh, Yuh-Pyng Sher
Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS...
January 24, 2024: Nature Cancer