JP1 suppresses proliferation and metastasis of melanoma through MEK1/2 mediated NEDD4L-SP1-Integrin αvβ3 signaling.

ABSTRACT: Background: JWA gene is known to down-regulate SP1 and reduces the expression level of Integrin αvβ3. Here, we identified a functional polypeptide (JP1) based on the active fragment of the JWA protein to suppress melanoma growth and metastasis by inhibiting the Integrin αvβ3. Methods: We conducted a series of melanoma growth and metastasis mouse models to evaluate anti-melanoma effect of JP1 peptide. ¹⁸F-labeled JP1 (¹⁸F-NFP-JP1) was detected by Micro-PET assay to demonstrate drug biodistribution. Toxicity test in cynomolgus monkeys and pharmacokinetic studies in rats were done to assess the druggability. The expression of MEK1/2, NEDD4L, SP1 and Integrin αvβ3 were detected in vitro and vivo models. Results: The peptide JP1 with the

SUBMITTER: Cui J 

PROVIDER: S-EPMC7381750 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature