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Establishment of inhibitory peptide for DKK3 functional domain, which inhibit Akt activation and consequent cellular proliferation, migration, and invasion in head and neck squamous cell carcinoma (HNSCC)

A research group led by Dr. Naoki Katase, Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University, has established an inhibitory peptide for DKK3 functional domain that can suppress the proliferation, migration, and invasion in HNSCC cells. Their findings were published in Cancer Cell International, an international journal of oncology. For the details of this research, refer to the journal below.

Dr. Katase and his colleagues have previously reported that DKK3 functions as tumor promoting factor which activates Akt phosphorylation and consequently elevates cancer cell proliferation, migration, and invasion in HNSCC cells, and that DKK3 gene has two start codons and can code both secreted protein and non-secreted protein, and both of them independently activate Akt signaling. Then, they conceived of antisense peptide that can inhibit protein-protein interaction of the both isoforms of DKK3.

■Methods and results 
They focused on the cysteine rich domain (CRD1 and CRD2) of DKK3 as a candidate for its functional domain. Deletion mutant expression plasmids were generated and transfected into HNSCC-derived cells, and it was shown that both of CRD1 and CRD2 are important for exertion of DKK3 function. Then, antisense peptides for the core amino acid sequences of CRD1 and CRD2 were designed.
Application of the antisense peptides in 100nM resulted in significantly reduced Akt phosphorylation, cellular proliferation, migration, and invasion in HNSCC-derived cells. Animal experiments revealed that the peptides could suppress the in vivo tumor growth of the HNSCC-derived cells in the xenograft model.

In conclusion, they have established a DKK3 specific inhibitory peptide that can suppress tumor proliferation, migration, and invasion at low doses. We will continue to investigate the application of this peptide in a clinical setting.

Establishment of anti-DKK3 peptide for the cancer control in head and neck squamous cell carcinoma (HNSCC).
Katase N, Nishimatsu SI, Yamauchi A, Okano S, Fujita S. Cancer Cell Int. 2022 Nov 15;22(1):352.
D O I:10.1186/s12935-022-02783-9.
U R L: https://cancerci.biomedcentral.com/articles/10.1186/s12935-022-02783-9

This study was supported by a Grant‐in‐Aid for Scientific Research (C) (Grant nos. 16K11470 and 20K09908) from MEXT KAKENHI and the Takeda Science Foundation (Grant no. 2018047114 to NK).