Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy

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Standard

Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy. / Lim, Yi Chieh; Jensen, Kamilla E.; Aguilar-Morante, Diana; Vardouli, Lina; Vitting-Seerup, Kristoffer; Gimple, Ryan C.; Wu, Qiulian; Pedersen, Henriette; Elbaek, Kirstine J.; Gromova, Irina; Ihnatko, Robert; Kristensen, Bjarne W.; Petersen, Jeanette K.; Skjoth-Rasmussen, Jane; Flavahan, William; Rich, Jeremy N.; Hamerlik, Petra.

I: Neuro-Oncology, Bind 25, Nr. 2, 2023, s. 248-260.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Lim, YC, Jensen, KE, Aguilar-Morante, D, Vardouli, L, Vitting-Seerup, K, Gimple, RC, Wu, Q, Pedersen, H, Elbaek, KJ, Gromova, I, Ihnatko, R, Kristensen, BW, Petersen, JK, Skjoth-Rasmussen, J, Flavahan, W, Rich, JN & Hamerlik, P 2023, 'Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy', Neuro-Oncology, bind 25, nr. 2, s. 248-260. https://doi.org/10.1093/neuonc/noac135

APA

Lim, Y. C., Jensen, K. E., Aguilar-Morante, D., Vardouli, L., Vitting-Seerup, K., Gimple, R. C., Wu, Q., Pedersen, H., Elbaek, K. J., Gromova, I., Ihnatko, R., Kristensen, B. W., Petersen, J. K., Skjoth-Rasmussen, J., Flavahan, W., Rich, J. N., & Hamerlik, P. (2023). Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy. Neuro-Oncology, 25(2), 248-260. https://doi.org/10.1093/neuonc/noac135

Vancouver

Lim YC, Jensen KE, Aguilar-Morante D, Vardouli L, Vitting-Seerup K, Gimple RC o.a. Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy. Neuro-Oncology. 2023;25(2):248-260. https://doi.org/10.1093/neuonc/noac135

Author

Lim, Yi Chieh ; Jensen, Kamilla E. ; Aguilar-Morante, Diana ; Vardouli, Lina ; Vitting-Seerup, Kristoffer ; Gimple, Ryan C. ; Wu, Qiulian ; Pedersen, Henriette ; Elbaek, Kirstine J. ; Gromova, Irina ; Ihnatko, Robert ; Kristensen, Bjarne W. ; Petersen, Jeanette K. ; Skjoth-Rasmussen, Jane ; Flavahan, William ; Rich, Jeremy N. ; Hamerlik, Petra. / Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy. I: Neuro-Oncology. 2023 ; Bind 25, Nr. 2. s. 248-260.

Bibtex

@article{0682a263b7f945a3abc0d109368d23b6,
title = "Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy",
abstract = "Background Glioblastoma (GBM) is a highly lethal malignancy for which neoangiogenesis serves as a defining hallmark. The anti-VEGF antibody, bevacizumab, has been approved for the treatment of recurrent GBM, but resistance is universal. Methods We analyzed expression data of GBM patients treated with bevacizumab to discover potential resistance mechanisms. Patient-derived xenografts (PDXs) and cultures were interrogated for effects of phosphofructokinase-1, muscle isoform (PFKM) loss on tumor cell motility, migration, and invasion through genetic and pharmacologic targeting. Results We identified PFKM as a driver of bevacizumab resistance. PFKM functions dichotomize based on subcellular location: cytosolic PFKM interacted with KIF11, a tubular motor protein, to promote tumor invasion, whereas nuclear PFKM safeguarded genomic stability of tumor cells through interaction with NBS1. Leveraging differential transcriptional profiling, bupivacaine phenocopied genetic targeting of PFKM, and enhanced efficacy of bevacizumab in preclinical GBM models in vivo. Conclusion PFKM drives novel molecular pathways in GBM, offering a translational path to a novel therapeutic paradigm.",
keywords = "bevacizumab, DNA damage and repair, invasion, PFKM, ENDOTHELIAL GROWTH-FACTOR, MIGRATION, CELLS, GLYCOLYSIS, PATHWAY, DISEASE, PREDICT, TRIAL",
author = "Lim, {Yi Chieh} and Jensen, {Kamilla E.} and Diana Aguilar-Morante and Lina Vardouli and Kristoffer Vitting-Seerup and Gimple, {Ryan C.} and Qiulian Wu and Henriette Pedersen and Elbaek, {Kirstine J.} and Irina Gromova and Robert Ihnatko and Kristensen, {Bjarne W.} and Petersen, {Jeanette K.} and Jane Skjoth-Rasmussen and William Flavahan and Rich, {Jeremy N.} and Petra Hamerlik",
year = "2023",
doi = "10.1093/neuonc/noac135",
language = "English",
volume = "25",
pages = "248--260",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy

AU - Lim, Yi Chieh

AU - Jensen, Kamilla E.

AU - Aguilar-Morante, Diana

AU - Vardouli, Lina

AU - Vitting-Seerup, Kristoffer

AU - Gimple, Ryan C.

AU - Wu, Qiulian

AU - Pedersen, Henriette

AU - Elbaek, Kirstine J.

AU - Gromova, Irina

AU - Ihnatko, Robert

AU - Kristensen, Bjarne W.

AU - Petersen, Jeanette K.

AU - Skjoth-Rasmussen, Jane

AU - Flavahan, William

AU - Rich, Jeremy N.

AU - Hamerlik, Petra

PY - 2023

Y1 - 2023

N2 - Background Glioblastoma (GBM) is a highly lethal malignancy for which neoangiogenesis serves as a defining hallmark. The anti-VEGF antibody, bevacizumab, has been approved for the treatment of recurrent GBM, but resistance is universal. Methods We analyzed expression data of GBM patients treated with bevacizumab to discover potential resistance mechanisms. Patient-derived xenografts (PDXs) and cultures were interrogated for effects of phosphofructokinase-1, muscle isoform (PFKM) loss on tumor cell motility, migration, and invasion through genetic and pharmacologic targeting. Results We identified PFKM as a driver of bevacizumab resistance. PFKM functions dichotomize based on subcellular location: cytosolic PFKM interacted with KIF11, a tubular motor protein, to promote tumor invasion, whereas nuclear PFKM safeguarded genomic stability of tumor cells through interaction with NBS1. Leveraging differential transcriptional profiling, bupivacaine phenocopied genetic targeting of PFKM, and enhanced efficacy of bevacizumab in preclinical GBM models in vivo. Conclusion PFKM drives novel molecular pathways in GBM, offering a translational path to a novel therapeutic paradigm.

AB - Background Glioblastoma (GBM) is a highly lethal malignancy for which neoangiogenesis serves as a defining hallmark. The anti-VEGF antibody, bevacizumab, has been approved for the treatment of recurrent GBM, but resistance is universal. Methods We analyzed expression data of GBM patients treated with bevacizumab to discover potential resistance mechanisms. Patient-derived xenografts (PDXs) and cultures were interrogated for effects of phosphofructokinase-1, muscle isoform (PFKM) loss on tumor cell motility, migration, and invasion through genetic and pharmacologic targeting. Results We identified PFKM as a driver of bevacizumab resistance. PFKM functions dichotomize based on subcellular location: cytosolic PFKM interacted with KIF11, a tubular motor protein, to promote tumor invasion, whereas nuclear PFKM safeguarded genomic stability of tumor cells through interaction with NBS1. Leveraging differential transcriptional profiling, bupivacaine phenocopied genetic targeting of PFKM, and enhanced efficacy of bevacizumab in preclinical GBM models in vivo. Conclusion PFKM drives novel molecular pathways in GBM, offering a translational path to a novel therapeutic paradigm.

KW - bevacizumab

KW - DNA damage and repair

KW - invasion

KW - PFKM

KW - ENDOTHELIAL GROWTH-FACTOR

KW - MIGRATION

KW - CELLS

KW - GLYCOLYSIS

KW - PATHWAY

KW - DISEASE

KW - PREDICT

KW - TRIAL

U2 - 10.1093/neuonc/noac135

DO - 10.1093/neuonc/noac135

M3 - Journal article

C2 - 35608632

VL - 25

SP - 248

EP - 260

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 2

ER -

ID: 345417830