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DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF‐A expression
Author(s) -
Yoon Nal Ae,
Jung Se Jin,
Choi Seong Hee,
Ryu Jin Hyun,
Mani Muralidharan,
Lee Unn Hwa,
Vo MaiTram,
Jeon Do Yong,
Chung Su Wol,
Ju Lee Byung,
Koh Young Wha,
Park Soon Eun,
Shin Yong Joon,
Kang Sang Soo,
Cho Wha Ja,
Cha Hee Jeong,
Park Jeong Woo
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15125
Subject(s) - melanoma , cancer research , vascular endothelial growth factor , metastasis , medicine , regulator , vegf receptors , lung , pathology , biology , cancer , gene , biochemistry
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.