MUC1 Protein Induces Urokinase-type Plasminogen Activator (uPA) by Forming a Complex with NF-κB p65 Transcription Factor and Binding to the uPA Promoter, Leading to Enhanced Invasiveness of Cancer Cells

Mori, Yoshihide; Akita, Kaoru; Tanida, Shuhei; Ishida, Akiko; Toda, Munetoyo; Inoue, Mizue; Yashiro, Masakazu; Sawada, Tetsuji; Hirakawa, Kosei

doi:10.1074/jbc.m114.586461

Cited by 34 publications

(32 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MUC1 suppresses activation of the ARF-MDM2-p53 pathway (39). In MUC1-expressing cells, a MUC1 co-operating NF-κB signaling pathway plays a critical role in cancer cell invasion (40). MUC1 deficiency impairs NFKB p65, Akt and MAPK pathways, which indicated that MUC1 appears to be a good therapeutic target to slow down esophageal tumor progression (41).…”

Section: Discussionmentioning

confidence: 99%

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

Abstract. MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Human MUC1 gene transfectants (HCT116/MUC1 and A549/ MUC1) and the respective control cells (HCT116/Mock and A549/Mock) were prepared as described previously (34). Human MUC1 gene knockdown cells (SKOV3/Si-1 and -2) and MUC1-expressing cells (SKOV3/Scr) were generated as described previously (35). Human galectin-3 gene knockdown HCT116/MUC1 cells (HCT116/MUC1-Gal-3/Si) and control cells (HCT116/MUC1-Scr) were generated by introducing human galectin-3 shRNA and scrambled shRNA vectors (InvivoGen, San Diego, CA), respectively, into HCT116/MUC1 cells.…”

Section: Methodsmentioning

confidence: 99%

“…Preparation of Total RNA and DNA Microarray AnalysisPreparation of total RNA and DNA microarray analysis were performed as described previously (35).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Binding of Galectin-3, a β-Galactoside-binding Lectin, to MUC1 Protein Enhances Phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and Akt, Promoting Tumor Cell Malignancy

Mori

Akita

Yashiro

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Both MUC1 and galectin-3 are overexpressed in various malignant tumors. Results: Binding of galectin-3 to MUC1 enhances the phosphorylation of ERK1/2 and Akt, promoting tumor cell malignancy. Conclusion: MUC1-mediated signal transduction occurs through direct binding of galectin-3 to MUC1. Significance: Our findings will provide a new insight into the promotion of MUC1-mediated tumor cell malignancy.

show abstract

“…These findings indicated the potential role of this molecule in the occurrence and progression of prostate cancer. Limited information is available on the association between HOTAIR and MUC1; however, other studies have reported on the involvement of the links of HOTAIR and MUC1 to NF-κB were found in oncogenic signaling pathways and tumor progression [34,35].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

Xiang

Zou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, reportedly exhibits antitumor effects. However, the detailed mechanism underlying PPI, particularly in enhancing the effect of the androgen receptor inhibitor enzalutamide in controlling castration-resistant prostate cancer (CRPC) has not been explored. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) expression was measured by quantitative real time-PCR (qRT-PCR). Western blot analysis was performed to determine the protein expression levels of MUC1, p65, and p50. Silencing of HOTAIR was evaluated using the siRNA procedure. The promoter activity of the MUC1 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expression of HOTAIR, p65, and MUC1 was conducted by transient transfection assay. A xenograft tumor model in nude mice was used to further evaluate the effect of the combination of PPI and enzalutamide in vivo. Results: We showed that PPI significantly inhibited growth and induced cell cycle arrest in CRPC cells. PPI also decreased p65 and MUC1 protein expression and reduced HOTAIR expression. Exogenously expressed p65 resisted the PPI-inhibited expression of HOTAIR, whereas silenced HOTAIR reduced MUC1 protein but exerted no effect on the expression of p65 and p50 proteins. Conversely, exogenously expressed HOTAIR resisted the PPI-inhibited MUC1 protein expression, and excessive expression of MUC1 antagonized the PPI-inhibited cell growth. Notably, PPI combined with enzalutamide exerted a synergistic effect. Consistent with this finding, PPI inhibited tumor growth, HOTAIR expression, as well as p65 and MUC1 protein expressions in vivo. Conclusions: Our results indicate that PPI inhibits the growth of CRPC cells by inhibiting p65 protein and concomitantly reducing HOTAIR expression, thereby suppressing MUC1 gene expression. The novel regulatory interaction of p65 and HOTAIR converge in the inhibition of MUC1 expression and overall PPI response. The combination of PPI and enzalutamide exhibits synergy. This study reveals a novel mechanism underlying the synergistic inhibitory effect of PPI and enzalutamide on the growth of CRPC cells.

show abstract

MUC1 Protein Induces Urokinase-type Plasminogen Activator (uPA) by Forming a Complex with NF-κB p65 Transcription Factor and Binding to the uPA Promoter, Leading to Enhanced Invasiveness of Cancer Cells

Cited by 34 publications

References 52 publications

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

Binding of Galectin-3, a β-Galactoside-binding Lectin, to MUC1 Protein Enhances Phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and Akt, Promoting Tumor Cell Malignancy

Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment

Contact Info

Product

Resources

About