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Targeting HIF-1/SEPT9_v1 complex to inhibit tumor growth and angiogenesis
Principle Investigator: Nicola J. Mabjeesh, MD, PhD
Background, highlight & our innovation: HIF-1 is the key player in the signaling
and survival of normal and cancer cells at low oxygen levels (hypoxia). Targeting of
the HIF system to exact a therapeutic response for the treatment of cancer is currently
one the most attractive targets in pharmaceutical development. We and others have
previously shown that the HIF pathway is “druggable” and has therapeutic utility as
an antitumor strategy.
We recently discovered a new regulator of the hypoxic response pathway in cancer
cells. This regulator (SEPT9_v1 ) is a member of the “obscure” mammalian septin
family. Our investigations during the past years show that HIF-1/SEPT9_v1
interaction has a significant role in tumorigenesis and angiogenesis and that disruption
of this complex is a likely point of significant intervention for cancer therapeutics.
This is a novel discovery from our lab which has been intensively studied here.
Applications: Manipulations of HIF-1/SEPT9_v1 complex could serve as a
therapeutic tool for cancer on the one hand and for ischemic diseases on the other
hand.
Publications:
1. Amir S, Mabjeesh NJ. SEPT9_v1 protein expression is associated with human
cancer cell resistance to microtubule-disrupting agents. Cancer Biol Ther. 2007
Dec;6(12):1926-31.
2. Amir S, Wang R, Matzkin H, Simons JW, Mabjeesh NJ. MSF-A interacts with
hypoxia-inducible factor-1alpha and augments hypoxia-inducible factor
transcriptional activation to affect tumorigenicity and angiogenesis.
Cancer Res. 2006 Jan 15;66(2):856-66.
Patent application is currently in national phase