Targeting the Intracellular MUC1 C-terminal Domain Inhibits Proliferation and Estrogen Receptor Transcriptional Activity in Lung Adenocarcinoma Cells

Abstract

Mucin 1 (MUC1) is a diagnostic factor and therapy target in lung adenocarcinoma. MUC1 C-terminal intracellular domain (CD) interacts with estrogen receptor α (ERα) and increases gene transcription in breast cancer cells. Because lung adenocarcinoma cells express functional ERα and estrogen receptor β (ERβ) we examined MUC1 expression and MUC1-ER interaction. Since blocking MUC1 CD with an inhibitory peptide (PMIP) inhibited breast tumor growth, we tested whether PMIP would inhibit lung adenocarcinoma cell proliferation. We report that MUC1 interacts with ERα and ERβ within the nucleus of H1793 lung adenocarcinoma cells in accordance with MUC1 expression. PMIP was taken up by H23 and H1793 cells and inhibited the proliferation of H1793, but not H23 cells, concordant with higher MUC1 in H1793 cells. Lower MUC1 protein in H23 does not correspond to miR-125b and miR-145 that have been reported to reduce MUC1 expression. PMIP had no effect on the viability of normal human bronchial epithelial cells, which lack MUC1 expression. PMIP inhibited estradiol (E2) –activated reporter gene transcription and endogenous cyclin D1 and nuclear respiratory factor-1 (NRF-1) gene transcription in H1793 cells. These results indicate MUC1-ER functional interaction in lung adenocarcinoma cells and that inhibiting MUC1 inhibits lung adenocarcinoma cell viability.

Near‐Infrared Afterglow Semiconducting Nano‐Polycomplexes for the Multiplex Differentiation of Cancer Exosomes

“…Zuschriften MCF7-secreted exosomes expressed the highest levels of MUC1, HER2, and EpCAM, while the highest expression level of CD63 was found in HeLa-secreted exosomes.T hese findings were consistent with previous reports showing ad rastically upregulated transcription level of cellular MUC1 in MCF-7 [16] and exosomal CD63 in HeLa. [10b] These data also verify the capability of ASPNC to differentiate the subtle variation of protein levels in exosomes from different source cells.…”

MUC1 and metastatic cancer

“…113 Follow-up studies with PMIP further demonstrated the utility of PMIP as a therapeutic intervention for lung cancer, although neither of these studies focused on metastatic disease. 114,115 In the Kufe laboratory, the ability of MUC1-CD to form dimers was targeted with a peptide-based therapy termed GO-203. 116 GO-203 is a decoy peptide conjugated to the cell penetrating peptide and targeted to the juxtamembrane region of MUC1, which serves as both the non-canonical nuclear conjugated to a MUC1-GST fusion protein (M-FP), or seven injections of placebo after mastectomy.…”

MUC1 and C-Met Affect Proliferation, Intercellular Junctions and Invasion in Two Head and Neck Carcinoma Cell Lines

“…MUC1 for example is a prognostic indicator in gastric and colorectal cancer and a marker of progression and metastasis [6]. Inhibition of MUC1 affects its oligomerization domain and signaling in prostate cancer, lung adenocarcinoma, and breast cancer [15][16][17]. Interaction of MUC1/c-Met has been associated with high motility and invasion in pancreatic adenocarcinoma [18].…”