CDKL3 Targets ATG5 to Exacerbate the Progression of Malignant Melanoma.

Abstract

Melanoma is a type of skin cancer originating from melanocytes with a high risk of gastrointestinal tract metastasis. The abnormal expression of cyclin-dependent kinase-like 3 (CDKL3) is involved in several tumor progression. However, the role of CDKL3 in malignant melanoma has never been reported and remains unknown. In this study, the expression of CDKL3 was revealed using clinical human malignant melanoma tissues and normal skin tissues. The effects of CDKL3 on malignant melanoma cell phenotypes was evaluated in vitro and in vivo via establishing CDKL3 deficiency cell models. Our results indicated that CDKL3 was highly expressed in malignant melanoma tissues, especially in advanced malignant melanoma tissues, in comparison with normal skin tissues. Moreover, CDKL3 knockdown significantly suppressed the proliferation, migration and invasion of malignant melanoma cells, and induced cell apoptosis. The indispensable role of CDKL3 on tumorigenesis was confirmed through in vivo experiments. Finally, we showed that CDKL3 promoted malignant melanoma progression via targeting autophagy related 5 (ATG5). CDKL3 induced melanoma cell autophagy through an ATG5-dependent manner. In conclusion, these results showed the promoting role of CDKL3 in proliferation and migration of malignant melanoma cells. The CDKL3 may be a novel biomarker for malignant melanoma progression and the potential therapeutic target for patients with malignant melanoma.