PHIP drives glioblastoma motility and invasion by regulating the focal adhesion complex
David de Semir, Vladimir Bezrookove, Mehdi Nosrati, Kara R. Scanlon, Eric A. Singer, Jonathon Judkins, Christopher Rieken, Clayton Wu, Julia Shen, Christina Schmudermayer, Altaf A. Dar, James R. Miller, Charles Cobbs, Garret Yount, Pierre‐Yves Desprez, Robert J. Debs, Nathan Salomonis, Sean D. McAllister, James E. Cleaver, Liliana Soroceanu, Mohammed Kashani–Sabet
Abstract
Significance Glioblastoma has an extremely poor prognosis, driven by its invasive and angiogenic potential. The development of effective therapies for glioblastoma will require the identification of molecular factors that promote these hallmarks. Our results show that PHIP drives glioblastoma motility, invasion, and angiogenesis. These functions are enabled by localization of PHIP to focal adhesions. PHIP regulates expression of focal adhesion proteins and physically interacts with vinculin, mechanisms by which it promotes tumor cell motility and invasion. The presence of elevated PHIP copy number in distinct molecular glioblastoma subtypes provides additional support for its importance to glioblastoma biology. These studies also identify PHIP as a compelling target for glioblastoma therapy.