LOSS OF PRIMARY CILIA PROMOTES AUTOPHAGIC DEGRADATION OF CBL AND SUSTAINS EGFR SIGNALING IN CHOLANGIOCYTES (AASLD 2026) - Oct 6, 2026 - Abstract #1016; Pres time: Nov 5, 2026; 12:00 PM - 01:00 PM; Location: Convention Center: Poster Hall, Hall DE; "Autophagydependent degradation pathways were assessed using chloroquine, mefloquine, and siRNA targeting ATG5 and the selective autophagy receptor NBR1...Restoration of ciliogenesis was induced using the HDAC6 inhibitor ACY1215 or HDAC6-shRNA in HuCCT1 cells and an orthotopic rat model of CCA... This study identifies a novel mechanism linking primary cilia dysfunction to sustained EGFR signaling through autophagy-dependent degradation of CBL in cholangiocytes and cholangiocarcinoma. Loss of cilia promotes selective autophagic clearance of CBL, impairing EGFR degradation and prolonging oncogenic signaling. Restoration of ciliogenesis through HDAC6 inhibition, or blockade of autophagy, rescues CBL-mediated EGFR regulation and suppresses tumor growth."
Biliary Cancer • Cholangiocarcinoma • Hematological Malignancies • Lymphoma • Solid Tumor • Targeted Protein Degradation • ATG5 • CBL
|
|
Kishor Pant1; Estanislao Peixoto2; Seth Richard3; Branko Dubravcic3; Naheed Arfin Borah3; Sergio Gradilone4
|