期刊
ONCOTARGET
卷 5, 期 15, 页码 6387-6403出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2201
关键词
high mobility group box 1; p53; p21; Sp1; melanoma
资金
- National Natural Science Foundation of China [81001217, 81225013]
- Graduate Innovation Project in Hunan Province [CX2013B107]
Although laboratory studies have implicated the high mobility group box 1 (HMGB1) in melanoma, its clinical relevance remains unclear. We analyzed nearly 100 cases of human melanoma and found that HMGB1 was highly overexpressed in melanoma samples relative to normal skin and nevi tissues. Significantly, higher levels of HMGB1 correlated with more advanced disease stages and with poorer survival in melanoma patients. Unlike the well-documented pro-inflammatory role of the extracellular HMGB1, we found that its intracellular activity is necessary for melanoma cell proliferation. An absolute dependency of melanoma cell proliferation on HMGB1 was underscored by the marked response of cell cycle arrest and senescence to HMGB1 knockdown. We demonstrated that HMGB1 deficiency-induced inhibition of cell proliferation was mediated by p21, which was induced via a Sp1-dependent mechanism. Taken together, our data demonstrate a novel oncogenic role of HMGB1 in promoting human melanoma cell proliferation and have important implications in melanoma patient care.
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