RRC ID 52248
Author Fukushima S, Endo M, Matsumoto Y, Fukushi JI, Matsunobu T, Kawaguchi KI, Setsu N, IIda K, Yokoyama N, Nakagawa M, Yahiro K, Oda Y, Iwamoto Y, Nakashima Y.
Title Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor.
Journal PLoS One
Abstract BACKGROUND:Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear.
METHODS:The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α.
RESULTS:The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis.
CONCLUSION:Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs.
Volume 12(5)
Pages e0178064
Published 2017-5-30
DOI 10.1371/journal.pone.0178064
PII PONE-D-17-00673
PMID 28558056
PMC PMC5448771
MeSH Cell Line, Tumor Cell Proliferation Female Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Male Middle Aged Neurilemmoma / metabolism* Neurilemmoma / pathology Neurilemmoma / therapy Oxygen / metabolism Polymerase Chain Reaction Prognosis RNA, Small Interfering / genetics
IF 2.74
Times Cited 7
Human and Animal Cells HS-Sch-2(RCB2230)