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J Vet Med Sci ; 85(9): 977-984, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37495516

ABSTRACT

Melanoma is a highly aggressive and metastatic cancer occurring in both humans and dogs. Canine melanoma accounts for a significant proportion of neoplastic diseases in dogs, and despite standard treatments, overall survival rates remain low. Protein phosphatase 6 (PP6), an evolutionarily conserved serine/threonine protein phosphatase, regulates various biological processes. Additionally, the loss of PP6 function reportedly leads to the development of melanoma in humans. However, there are no reports regarding the role of PP6 in canine cancer cells. We, therefore, conducted a study investigating the role of PP6 in canine melanoma by using four canine melanoma cell lines: CMec1, CMM, KMeC and LMeC. PP6 knockdown increased phosphorylation levels of mitogen-activated protein kinase kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2) but not Akt. Furthermore, PP6 knockdown decreased sensitivity to trametinib, a MEK inhibitor, but did not alter sensitivity to Akt inhibitor. These findings suggest that PP6 may function as a tumor suppressor in canine melanoma and modulate the response to trametinib treatment. Understanding the role of PP6 in canine melanoma could lead to the development of more effective treatment strategies for this aggressive disease.


Subject(s)
Dog Diseases , Melanoma , Animals , Dogs , Humans , MAP Kinase Kinase 1/metabolism , MAP Kinase Kinase 1/pharmacology , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 3/pharmacology , MAP Kinase Signaling System , Phosphoprotein Phosphatases/metabolism , Phosphoprotein Phosphatases/pharmacology , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Melanoma/drug therapy , Melanoma/veterinary , Cell Line, Tumor , Dog Diseases/drug therapy
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