Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma

Joint Authors

Xia, Qinghua
Xu, Yingkun
Li, Jianyi
Wu, Guangzhen
Li, Jiatong
Ruan, Ningke
Chen, Yougen
Zhang, Qi

Source

BioMed Research International

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-16, 16 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-02-13

Country of Publication

Egypt

No. of Pages

16

Main Subjects

Medicine

Abstract EN

Targeted therapy for kidney cancer has achieved significant clinical results.

However, because most patients who use targeted therapy will develop drug resistance, we still need to constantly explore new therapeutic targets.

Although porcupine (PORCN) as a palmitoyltransferase plays a crucial role in the activation and secretion of Wnt proteins and affects the activity of the Wnt signaling pathway, little is known about the role of PORCN in clear cell renal cell carcinoma (ccRCC).

We found that PORCN is highly expressed in renal cancer cell lines and patients with renal cell carcinoma with high expression of PORCN have a poor prognosis.

Pathway analysis of PORCN and its related proteins showed that PORCN played a role through the Wnt signaling pathway, and there was a strong coexpression relationship between PORCN and Wnt proteins.

Therefore, PORCN may be a potential and effective target for ccRCC.

In the present study, we found that LGK974 could inhibit proliferation and colony formation and induce apoptosis in ccRCC cells.

We also found that LGK974 could inhibit the migration and invasion of renal cell carcinoma and reduce the expression of mesenchymal markers.

After treatment with LGK974, the expression level of β-catenin, a key protein in the classical Wnt pathway, was significantly decreased, and the expression levels of the target genes cyclin D1, c-Myc, MMP9, and MMP2 in the Wnt signaling pathway were also significantly decreased, which represented a significant decrease in the activity of the Wnt signaling pathway.

At the same time, the cycle of renal cancer cells was significantly blocked.

In conclusion, our results indicate that LGK974 could significantly inhibit the progression of renal cancer cells in a safe concentration range, so PORCN may be a safe and effective target for patients with renal cancer.

American Psychological Association (APA)

Li, Jianyi& Wu, Guangzhen& Xu, Yingkun& Li, Jiatong& Ruan, Ningke& Chen, Yougen…[et al.]. 2020. Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma. BioMed Research International،Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1132566

Modern Language Association (MLA)

Li, Jianyi…[et al.]. Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma. BioMed Research International No. 2020 (2020), pp.1-16.
https://search.emarefa.net/detail/BIM-1132566

American Medical Association (AMA)

Li, Jianyi& Wu, Guangzhen& Xu, Yingkun& Li, Jiatong& Ruan, Ningke& Chen, Yougen…[et al.]. Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1132566

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1132566