American Association for Cancer Research
Browse
- No file added yet -

Supplementary Figure S5ABC from Dependence on the MUC1-C Oncoprotein in Non–Small Cell Lung Cancer Cells

Download (1.62 MB)
journal contribution
posted on 2023-04-03, 13:26 authored by Deepak Raina, Michio Kosugi, Rehan Ahmad, Govind Panchamoorthy, Hasan Rajabi, Maroof Alam, Takeshi Shimamura, Geoffrey I. Shapiro, Jeffrey Supko, Surender Kharbanda, Donald Kufe
Supplementary Figure S5ABC from Dependence on the MUC1-C Oncoprotein in Non–Small Cell Lung Cancer Cells

History

ARTICLE ABSTRACT

Non–small cell lung cancer (NSCLC) cells are often associated with constitutive activation of the phosphoinositide 3-kinase (PI3K) → Akt → mTOR pathway. The mucin 1 (MUC1) heterodimeric glycoprotein is aberrantly overexpressed in NSCLC cells and induces gene signatures that are associated with poor survival of NSCLC patients. The present results show that the MUC1 C-terminal subunit (MUC1-C) cytoplasmic domain associates with PI3K p85 in NSCLC cells. We show that inhibition of MUC1-C with cell-penetrating peptides blocks this interaction with PI3K p85 and suppresses constitutive phosphorylation of Akt and its downstream effector, mTOR. In concert with these results, treatment of NSCLC cells with the MUC1-C peptide inhibitor GO-203 was associated with downregulation of PI3K → Akt signaling and inhibition of growth. GO-203 treatment was also associated with increases in reactive oxygen species (ROS) and induction of necrosis by a ROS-dependent mechanism. Moreover, GO-203 treatment of H1975 (EGFR L858R/T790M) and A549 (K-Ras G12S) xenografts growing in nude mice resulted in tumor regressions. These findings indicate that NSCLC cells are dependent on MUC1-C both for activation of the PI3K → Akt pathway and for survival. Mol Cancer Ther; 10(5); 806–16. ©2011 AACR.

Usage metrics

    Molecular Cancer Therapeutics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC