%0 Journal Article
%T MUC1-C Dependence for the Progression of Pancreatic Neuroendocrine Tumors Identifies a Druggable Target for the Treatment of This Rare Cancer.
%A Ozawa H
%A Haratake N
%A Nakashoji A
%A Daimon T
%A Bhattacharya A
%A Wang K
%A Shigeta K
%A Fushimi A
%A Fukuda K
%A Masugi Y
%A Yamaguchi R
%A Kitago M
%A Kawakubo H
%A Kitagawa Y
%A Kufe D
%J Biomedicines
%V 12
%N 7
%D 2024 Jul 8
%M 39062082
%F 4.757
%R 10.3390/biomedicines12071509
%X Patients with pancreatic neuroendocrine tumors (pNETs) have limited access to effective targeted agents and invariably succumb to progressive disease. MUC1-C is a druggable oncogenic protein linked to driving pan-cancers. There is no known involvement of MUC1-C in pNET progression. The present work was performed to determine if MUC1-C represents a potential target for advancing pNET treatment. We demonstrate that the MUC1 gene is upregulated in primary pNETs that progress with metastatic disease. In pNET cells, MUC1-C drives E2F- and MYC-signaling pathways necessary for survival. Targeting MUC1-C genetically and pharmacologically also inhibits self-renewal capacity and tumorigenicity. Studies of primary pNET tissues further demonstrate that MUC1-C expression is associated with (i) an advanced NET grade and pathological stage, (ii) metastatic disease, and (iii) decreased disease-free survival. These findings demonstrate that MUC1-C is necessary for pNET progression and is a novel target for treating these rare cancers with anti-MUC1-C agents under clinical development.