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- Title
MUC1-C Dependence for the Progression of Pancreatic Neuroendocrine Tumors Identifies a Druggable Target for the Treatment of This Rare Cancer.
- Authors
Ozawa, Hiroki; Haratake, Naoki; Nakashoji, Ayako; Daimon, Tatsuaki; Bhattacharya, Atrayee; Wang, Keyi; Shigeta, Keisuke; Fushimi, Atsushi; Fukuda, Kazumasa; Masugi, Yohei; Yamaguchi, Ryo; Kitago, Minoru; Kawakubo, Hirofumi; Kitagawa, Yuko; Kufe, Donald
- Abstract
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.
- Subjects
ONCOGENIC proteins; NEUROENDOCRINE tumors; PROGRESSION-free survival; DISEASE progression; TUMOR classification
- Publication
Biomedicines, 2024, Vol 13, Issue 7, p1509
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines12071509