WNK3 Promotes Neuronal Survival after Traumatic Brain Injury in Rats

Zhu, Jie; Lin, Xiaohui; Chen, Chen; Tan, Helian; Gao, Yanping; Li, Di; Chen, Gang

doi:10.1016/j.neuroscience.2021.09.021

Cited by 2 publications

(2 citation statements)

References 54 publications

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“…Ispinesib alone reaches maximum efficacy of 25%–20% viability (red solid curve lines), and the viability is further decreased with the addition of the second drug (blue dashed curve lines) ( Figures 5F – 5I ). WNK3, 44 – 46 RIOK1, 47 – 49 MYB, 50 , 51 and CTSF 52 may protect ispinesib-resistant cells from apoptosis or help ispinesib-resistant cells progress through cell cycle. Overall, these results demonstrate how lineage-tracing analysis by scRNA-seq can be used to identify drug combinations by identifying markers of resistant clones in the drug-naive setting.…”

Section: Resultsmentioning

confidence: 99%

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

Cheng,

Banu,

Zhao

et al. 2024

Cell Reports

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Section: Resultsmentioning

confidence: 99%

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

Cheng,

Banu,

Zhao

et al. 2024

Cell Reports

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“…Ispinesib alone reaches maximum efficacy of 25% to 20% viability (red solid curve lines), and the viability is further decreased with addition of the second drug (blue dash curve lines) (Figure 4F-4I). WNK3 [40][41][42] , RIOK1 [43][44][45] , MYB 46,47 and CTSF 48 may protect ispinesib-resistant cells from apoptosis or help ispinesib resistant cells progress through cell cycle. Overall, these results demonstrate how lineage tracing analysis by scRNA-seq can be used to identify novel drug combinations by identifying markers of resistant clones in the drug-naïve setting.…”

Section: Identification Of Synergistic Drug Targets From Gene Express...mentioning

confidence: 99%

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

Cheng,

Banu,

Zhao

et al. 2023

Preprint

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SUMMARYGlioblastoma (GBM) is a deadly brain tumor, and the kinesin motor KIF11 is an attractive therapeutic target because of its dual roles in proliferation and invasion. The clinical utility of KIF11 inhibitors has been limited by drug resistance, which has mainly been studied in animal models. We used multiplexed lineage tracing barcodes and scRNA-seq to analyze drug resistance time courses for patient-derived GBM neurospheres treated with ispinesib, a potent KIF11 inhibitor. Similar to GBM progression in patients, untreated cells lost their neural lineage identity and transitioned to a mesenchymal phenotype, which is associated with poor prognosis. In contrast, cells subjected to long-term ispinesib treatment exhibited a proneural phenotype. We generated patient-derived xenografts to show that ispinesib-resistant cells form less aggressive tumorsin vivo, even in the absence of drug. Finally, we used lineage barcodes to nominate drug combination targets by retrospective analysis of ispinesib-resistant clones in the drug-naïve setting and identified drugs that are synergistic with ispinesib.

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WNK3 Promotes Neuronal Survival after Traumatic Brain Injury in Rats

Cited by 2 publications

References 54 publications

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

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