Elucidating the role of DEPDC1B in melanoma development and metastasis

Abstract

Melanoma is considered the most malignant skin cancers because of its aggressiveness, therapeutic resistance, and metastasis as a late manifestation. The ineffectiveness of the current treatment regimen prompts us to identify new druggable targets in governing the systemic spread of melanoma. DEPDC1B has been shown to orchestrate oncogenic events in several cancer types, yet its roles in melanoma are not fully revealed. Analysis of the TCGA database reveals higher level of DEPDC1B expression is accompanied with lower survival rate of patients with skin cutaneous melanoma. In vitro functional assays including AlamarBlue, colony formation and trans-well invasion demonstrate that DEPDC1B functions as an oncogene in promoting melanoma proliferation and invasion. Consistently, mice xenograft and lung colonization assays further support the functional importance of DEPDC1B for melanoma tumorigenicity and metastasis. Moreover, conditioned medium from DEPDC1B overexpressing and knockdown cells promotes and reduces branching of HUVEC respectively. Altogether, the results obtained so far indicate that DEPDC1B is oncogenic in promoting melanoma growth and metastasis partly through regulating the secretion of pro-angiogenic factors to stimulate the branching or formation of blood vessels. Identification of pro-angiogenic factors and characterization of the oncogenic mechanisms by DEPDC1B in melanoma are currently ongoing.