Dipanjan Basu1, Cláudia M Salgado2, Bruce Bauer3, Yasmin Khakoo4,5, Janki R Patel6, Ryan M Hoehl6, Dominique M Bertolini6, Joie Zabec6, Morgan R Brzozowski6, Miguel Reyes-Múgica2. 1. Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, PA, U.S.A basud@upmc.edu. 2. Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, PA, U.S.A. 3. Division of Plastic and Reconstructive Surgery, North Shore University Health System, Northbrook, IL, U.S.A. 4. Department of Pediatrics and Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, U.S.A. 5. Department of Pediatrics, Weill Cornell Medical College, New York, NY, U.S.A. 6. Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, U.S.A.
Abstract
BACKGROUND: Omipalisib has been found to affect the viability of cancer cells. However, its effect on clonogenicity - a feature of cancer stem cells, is not clear. Cells isolated from neurocutaneous melanocytosis (NCM) patients' lesions grow clonogenically. The aim of this study was to investigate the effect of omipalisib treatment on clonogenic growth of NCM cells in vitro. MATERIALS AND METHODS: Clonogenic growth efficiency was evaluated by colony formation assays with or without specific growth factors. Activation of MEK and Akt was determined by immunoblots. Colony formation and cell viability were assessed upon pharmacological inhibition of MEK, Akt and mToR. RESULTS: Clonogenicity appeared to depend on bFGF and IGF1signaling through ERK and Akt. Omipalisib treatment prevented colony formation and induced autophagic cell death. CONCLUSION: Signaling through Akt is important for survival of clonogenic cells in NCM, and omipalisib treatment as a monotherapy or in combination with MEK162 could be an effective therapeutic strategy to inhibit clonogenic growth. Copyright
BACKGROUND:Omipalisib has been found to affect the viability of cancer cells. However, its effect on clonogenicity - a feature of cancer stem cells, is not clear. Cells isolated from neurocutaneous melanocytosis (NCM) patients' lesions grow clonogenically. The aim of this study was to investigate the effect of omipalisib treatment on clonogenic growth of NCM cells in vitro. MATERIALS AND METHODS: Clonogenic growth efficiency was evaluated by colony formation assays with or without specific growth factors. Activation of MEK and Akt was determined by immunoblots. Colony formation and cell viability were assessed upon pharmacological inhibition of MEK, Akt and mToR. RESULTS: Clonogenicity appeared to depend on bFGF and IGF1signaling through ERK and Akt. Omipalisib treatment prevented colony formation and induced autophagic cell death. CONCLUSION: Signaling through Akt is important for survival of clonogenic cells in NCM, and omipalisib treatment as a monotherapy or in combination with MEK162 could be an effective therapeutic strategy to inhibit clonogenic growth. Copyright
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