MUC1-C IS A MASTER REGULATOR OF MICA/B NKG2D LIGAND AND EXOSOME SECRETION IN HUMAN CANCER CELLS
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE215308 | GEO | 2022/10/17
REPOSITORIES: GEO
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Project description:MUC1-C IS A MASTER REGULATOR OF MICA/B NKG2D LIGAND AND EXOSOME SECRETION IN HUMAN CANCER CELLS
| PRJNA889743 | ENA
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Project description:Small cell lung cancer (SCLC) is a recalcitrant malignancy associated with dysregulation of MYC signaling and the CDK-RB-E2F axis. We report that expression of the oncogenic MUC1-C protein in SCLC cells integrates activation of MYC and the E2F pathway. MUC1-C drives MYC and E2F target genes and regulates the G2/M checkpoint, mitotic spindle pathway and replication stress response (RSR). We further show that MUC1-C MYC signaling (i) induces NOTCH2, a marker of pulmonary neuroendocrine (NE) stem cells that are the proposed cell of SCLC origin, (ii) drives NE differentiation, as evidenced by expression of ASCL1 and POU3F2/BRN2, and (iii) promotes self-renewal capacity and tumorigenicity of SCLC cells. Analyses of datasets from SCLC tumors confirmed that MUC1 significantly associates with the MYC pathway. These findings uncover a master role for MUC1-C in promoting progression of the SCLC stem cell state and support MUC1-C as a potential target for SCLC treatment.
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