z-logo
Premium
Hypoxia‐induced HIF 1 α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis
Author(s) -
Loftus Stacie K.,
Baxter Laura L.,
Cronin Julia C.,
Fufa Temesgen D.,
Pavan William J.
Publication year - 2017
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12579
Subject(s) - gene knockdown , melanocyte , hypoxia (environmental) , melanoma , biology , cancer research , gene expression , gene , gene expression profiling , genetics , chemistry , organic chemistry , oxygen
Summary Hypoxia and HIF 1 α signaling direct tissue‐specific gene responses regulating tumor progression, invasion, and metastasis. By integrating HIF 1 α knockdown and hypoxia‐induced gene expression changes, this study identifies a melanocyte‐specific, HIF 1 α ‐dependent/hypoxia‐responsive gene expression signature. Integration of these gene expression changes with HIF 1 α Ch IP ‐Seq analysis identifies 81 HIF 1 α direct target genes in melanocytes. The expression levels for 10 of the HIF 1 α direct targets – GAPDH , PKM , PPAT , DARS , DTWD 1 , SEH 1L , ZNF 292 , RLF , AGTRAP , and GPC 6 – are significantly correlated with reduced time of disease‐free status in melanoma by logistic regression (P ‐ value = 0.0013) and ROC curve analysis ( AUC  = 0.826, P‐value < 0.0001). This HIF 1 α ‐regulated profile defines a melanocyte‐specific response under hypoxia, and demonstrates the role of HIF 1 α as an invasive cell state gatekeeper in regulating cellular metabolism, chromatin and transcriptional regulation, vascularization, and invasion.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here