OTUD4 regulates metastasis and chemoresistance in melanoma by stabilizing Snail1

Abstract

Melanoma is the most aggressive form of skin cancer with rapidly increased incidence worldwide especially in the Caucasian population. Surgical excision represents the curative treatment choice in patients with early‐stage disease. However, the therapeutic outcomes in patients with metastatic melanoma remains unsatisfactory. Thus, understanding molecular mechanisms contributing to metastasis and chemoresistance is critical for new improved therapies of melanoma. Snail1, an important epithelial‐mesenchymal transition transcription factors (EMT‐TFs), is critical to induce the EMT process, thereby contributing to cancer metastasis. However, the involvement of Snail1 in melanoma metastasis remains elusive and the underlying mechanism to regulate Snail1 in melanoma needs to be further investigated. Here, we identified OTUD4 as a novel deubiquitinase of Snail1 in melanoma. Moreover, the depletion of OTUD4 in melanoma cells markedly inhibited Snail1 stability and Snail1‐driven malignant phenotypes both in vitro and in vivo. Overall, our study establishes OTUD4 as a novel therapeutic target in metastasis and chemoresistance of melanoma by stabilizing Snail1 and provides a rationale for potential therapeutic strategies of melanoma.

OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway

“…OTULIN maintains GSC self-renewal and is associated with poor prognosis in GBM [ 37 ]. As a member of the OTU family, OTUD4 has also been shown to affect cancer progression, for example, on the one hand, OTUD4 acts as an oncogene to facilitate the metastasis of triple-negative breast cancer [ 38 ] and melanoma [ 39 ]; on the other hand, OTUD4 acts as a tumor suppressor gene to inhibit the proliferation of liver cancer and non-small cell lung cancer, and regulate the radiosensitivity of nasopharyngeal carcinoma [ 40 ]. However, the effects of OTUD4 on GBM have not been reported.…”