Publication date: Aug 08, 2019
SHARPIN, as a tumor-associated gene, is involved in the metastatic process of many kinds of tumors. Herein, we studied the function of SHARPIN in melanoma metastasis and the relevant molecular mechanisms. We found that SHARPIN expression was increased in melanoma tissues and activated the process of proliferation, migration and invasion in vitro and in vivo, resulting in a poor prognosis of the disease. Functional analysis demonstrated that SHARPIN promoted melanoma migration and invasion by regulating Rap1 and its downstream pathways, including p38 and JNK/c-Jun. Rap1 activator (8-pCPT-2′-O-Me-cAMP) and inhibitor (ESI-09 and farnesylthiosalicylic acid-amide) treatments could partially rescue invasion and migration of tumor cells. Additionally, SHARPIN expression in cell lines and public datasets also indicated that molecules other than BRAF and N-RAS may contribute to SHARPIN activation. In conclusion, our broad-in-depth work suggested that SHARPIN promoted melanoma development via p38 and JNK/c-Jun pathways through upregulating Rap1 expression.
Zhou, S., Liang, Y., Zhang, X., Liao, L., Yang, Y., Ouyang, W., and Xu, H. SHARPIN Promotes Melanoma Progression via Rap1 Signaling Pathway. 23717. 2019 J Invest Dermatol.
|drug||DRUGBANK||Cyclic Adenosine Monophosphate|
|pathway||BSID||Rap1 signaling pathway|