{Reference Type}: Journal Article
{Title}: MUC1-C Dependence for the Progression of Pancreatic Neuroendocrine Tumors Identifies a Druggable Target for the Treatment of This Rare Cancer.
{Author}: Ozawa H;Haratake N;Nakashoji A;Daimon T;Bhattacharya A;Wang K;Shigeta K;Fushimi A;Fukuda K;Masugi Y;Yamaguchi R;Kitago M;Kawakubo H;Kitagawa Y;Kufe D;
{Journal}: Biomedicines
{Volume}: 12
{Issue}: 7
{Year}: 2024 Jul 8
{Factor}: 4.757
{DOI}: 10.3390/biomedicines12071509
{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.