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DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF-A expression.

The FEBS journal (2019-11-07)
Nal Ae Yoon, Se Jin Jung, Seong Hee Choi, Jin Hyun Ryu, Muralidharan Mani, Unn Hwa Lee, Mai-Tram Vo, Do Yong Jeon, Su Wol Chung, Byung Ju Lee, Young Wha Koh, Soon Eun Park, Yong Joon Shin, Sang Soo Kang, Wha Ja Cho, Hee Jeong Cha, Jeong Woo Park
ABSTRACT

Malignant metastatic melanoma (MM) is the most lethal of all skin cancers, but detailed mechanisms for regulation of melanoma metastasis are not fully understood. Here, we demonstrated that developmentally regulated GTP-binding protein 2 (DRG2) is required for the growth of primary tumors and for metastasis. DRG2 expression was significantly increased in MM compared with primary melanoma (PM) and dysplastic nevi. A correlation between DRG2 expression and poor disease-specific survival in melanoma patients was also identified. Furthermore, inhibition of DRG2 suppressed the binding of Hypoxia-inducible factor 1α to the VEGF-A promoter region, expression of vascular endothelial growth factor (VEGF)-A, and formation of endothelial cell tubes. In experimental mice, DRG2 depletion inhibited the growth of PM and lung metastases and increased survival. These results identify DRG2 as a critical regulator of VEGF-A expression and of growth of PMs and lung metastases.

MATERIALS
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Brand
Product Description

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