Targeting AVIL, a New Cytoskeleton Regulator in Glioblastoma

Cornelison, Robert; Marrah, Laine; Horter, Drew; Lynch, Sarah; Li, Hui

doi:10.3390/ijms222413635

Cited by 4 publications

(1 citation statement)

References 70 publications

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“…In addition to RMS, we have found that AVIL is overexpressed in many other sarcoma types, including Ewing, synovial, osteosarcoma, and liposarcoma. These and our previous finding that AVIL plays a critical role in glioblastoma (GBM) ( 20 – 22 ) suggest that AVIL may be a general oncogene, not limited to a particular cancer type.…”

Section: Discussionsupporting

confidence: 64%

Rhabdomyosarcomas are oncogene addicted to the activation of AVIL

Xie

Janczyk

Shi

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Rhabdomyosarcoma (RMS) is a common pediatric soft-tissue cancer. There are two main subtypes driven by distinct mechanisms. Currently, there is no targeted therapy for the disease. We found an oncogene AVIL, whose activity is often abnormally up-regulated in RMS. Silencing the gene kills RMS cells and prevents tumor formation in animals; yet, normal control cells are indifferent to the interference. Mechanistically, AVIL activation turns on both oncogene pathways in RMS. These findings support that AVIL may be a good therapeutic target and that targeting AVIL may be a viable approach for both types of RMS.

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Section: Discussionsupporting

confidence: 64%

Rhabdomyosarcomas are oncogene addicted to the activation of AVIL

Xie

Janczyk

Shi

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Flavopiridol Suppresses Cell Proliferation and Migration and Induces Apoptotic Cell Death by Inhibiting Oncogenic FOXM1 Signaling in IDH Wild-Type and IDH-Mutant GBM Cells

Guler,

Hamurcu,

Ulutabanca

et al. 2023

Mol Neurobiol

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Flavopiridol suppresses cell proliferation and migration and induces apoptotic cell death by inhibiting oncogenic FOXM1 signaling in IDH-wild type and -mutant GBM cells

Güler¹,

Hamurcu²,

Ulutabanca

et al. 2023

Preprint

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Glioblastoma multiforme (GBM) remains one of the most challenging solid cancers to treat due to its highly aggressive and drug resistant nature. Flavopiridol is synthetic flavone that was recently approved by the FDA for the treatment of acute myeloid leukemia. Flavopiridol exhibits antiproliferative activity in several solid cancer cells and currently evaluated in clinical trials in several solid and hematological cancers. In this study, we investigated the molecular mechanisms underlying antiproliferative effects of Flavopiridol in GBM cell lines with wild type and mutant IDH1 (encoding isocitrate dehydrogenase 1). We found that Flavopiridol inhibits proliferation, colony formation, migration, and induces apoptosis in IDH1-wild type and IDH-mutant cells through inhibition of FOXM1 oncogenic signaling. Furthermore, flavopiridol treatment also inhibits of NF-KB, mediators unfolded protein response (UPR) (GRP78, PERK, IRE1α) and DNA repair enzyme PARP, which have been shown, be potential therapeutic targets by downregulating FOXM1 in GBM cells. Our findings suggest for the first time that flavopiridol suppresses proliferation, survival and migration and induces apoptosis in IDH1-wild type and mutant GBM cells by targeting FOXM1 oncogenic signaling which also regulates NF-KB, PARP, UPR responsein GBM cells. Flavopiridol may be a potential novel therapeutic strategy in the treatment of patients IDH1-wild type and mutant GBM.

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Targeting AVIL, a New Cytoskeleton Regulator in Glioblastoma

Cited by 4 publications

References 70 publications

Rhabdomyosarcomas are oncogene addicted to the activation of AVIL

Rhabdomyosarcomas are oncogene addicted to the activation of AVIL

Flavopiridol Suppresses Cell Proliferation and Migration and Induces Apoptotic Cell Death by Inhibiting Oncogenic FOXM1 Signaling in IDH Wild-Type and IDH-Mutant GBM Cells

Flavopiridol suppresses cell proliferation and migration and induces apoptotic cell death by inhibiting oncogenic FOXM1 signaling in IDH-wild type and -mutant GBM cells

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