MSF-A interacts with hypoxia-inducible factor-1alpha and augments hypoxia-inducible factor transcriptional activation to affect tumorigenicity and angiogenesis.
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the signaling pathway that controls the hypoxic responses of cancer cells. Activation of the HIF system has been observed in carcinogenesis and numerous cancers. We found an interaction between a member of the mammalian septin gene family (MSF-A) and the HIF system. MSF-A is a nuclear protein that interacts with HIF-1alpha protein to prevent its ubiquitination and degradation, thus activating the HIF transcriptome. Cells overexpressing MSF-A protein exhibit increased HIF transcriptional activity and higher proliferation rates in vitro and in vivo. Xenograft-derived human tumors from these cells were larger and more vascular. These findings link a function of a septin protein with angiogenesis through activation of the HIF pathway.
Amir
Sharon
S
Prostate Cancer Research Laboratory, Department of Urology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239 Tel Aviv, Israel.
Wang
Ruoxiang
R
Matzkin
Haim
H
Simons
Jonathan W
JW
Mabjeesh
Nicola J
NJ
D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D020558:GTP Phosphohydrolases / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic; D011471:Prostatic Neoplasms / Q000473:pathology; D058112:Septins; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins