Back to Search
Start Over
MUC1-C Dependence for the Progression of Pancreatic Neuroendocrine Tumors Identifies a Druggable Target for the Treatment of This Rare Cancer
- Source :
- Biomedicines, Vol 12, Iss 7, p 1509 (2024)
- Publication Year :
- 2024
- Publisher :
- MDPI AG, 2024.
-
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 :
- MUC1-C
pNET
MYC
mTOR
NOTCH2
CSC
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 12
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Biomedicines
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0be1b7d4b33b43599c1834ba5fc9695b
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/biomedicines12071509