SHARPIN Promotes Melanoma Progression via Rap1 Signaling Pathway.

as a tumor-associated gene, is involved in the metastatic process of many kinds of tumors. Herein, we studied the function of Shank-associated RH domain interacting protein in melanoma metastasis and the relevant molecular mechanisms. We found that 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 SHduanyu37IN promoted melanoma migration and invasion by regulating Ras-associated protein-1(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, SHduanyu37IN expression in cell lines and public datasets also indicated that molecules other than BRAF and N-RAS may contribute to SHduanyu37IN activation. In conclusion, our broad-in-depth work suggests that SHduanyu37IN promotes melanoma development via p38 and JNK/c-Jun pathways through upregulation of Rap1 expression.

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