Inhibition of peptidyl-prolyl isomerase (PIN1) and BRAF signaling to target melanoma.
BRAF
PIN1
melanoma
peptide 37
proliferation
Journal
American journal of translational research
ISSN: 1943-8141
Titre abrégé: Am J Transl Res
Pays: United States
ID NLM: 101493030
Informations de publication
Date de publication:
2019
2019
Historique:
received:
04
07
2018
accepted:
01
10
2018
entrez:
10
8
2019
pubmed:
10
8
2019
medline:
10
8
2019
Statut:
epublish
Résumé
PIN1 is a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, overexpressed in many cancers, including melanoma. Our immunohistochemistry data of melanoma patient tissue underline the up-regulation of PIN1 in metastases. Here, we demonstrate important functions of PIN1 and its selective and cell permeable inhibitor 37 for the treatment of melanoma. To analyze its possible role in oncogenesis and as a therapeutic target, we first suppressed PIN1 expression by a siRNA pool. PIN1 knockdown potently inhibited melanoma cell proliferation and vascular mimicry by influencing several cancer-relevant pathways. Furthermore, inhibitor 37 inhibited cell growth in melanoma and induced apoptosis. Normal healthy melanocytes, keratinocytes and fibroblasts are not affected by the PIN1 inhibitor 37. Combinatorial treatment of melanoma cells is with Vemurafenib as a common therapeutic option for BRAF-mutated melanoma and inhibitor 37 resulted in a strong, synergistic effect on apoptosis of melanoma cell lines. In summary, targeting PIN1 offers a promising therapeutic approach to simultaneously downregulate multiple cancer-driving pathways in cancer.
Types de publication
Journal Article
Langues
eng
Pagination
4425-4437Déclaration de conflit d'intérêts
None.
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