Figure 3 from Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma Article Swipe

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Catherine A. Behrmann , Kelli N. Ennis , P.N. Sarma , Collin Wetzel , Nicholas A. Clark , Kate M. Von Handorf , Subrahmanya Vallabhapurapu , Cristina Andreani , James Reigle , Pier Paolo Scaglioni , Jarek Meller , Maria Czyzyk-Krzeska , Ady Kendler , Xiaoyang Qi , Jann N. Sarkaria , Mario Medvedovic , Soma Sengupta , Biplab Dasgupta , David R. Plas ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1158/2767-9764.26819635

S6K1 and AXL inhibitors counteract pyrimidine biosynthesis in PTEN-deficient GBM. A, Steady state metabolite abundance in LN229 GBM transfected with siPTEN and then treated with vehicle control or combination S6K1 (LY-2584702, 10 μmol/L) and AXL (BMS-777607, 10 μmol/L) inhibitors for 5 hours (n = 4). B, Detail of nucleotide and their precursor metabolites from A. C, log₂ fold change of [U]-¹³C glucose labeled metabolites in U87MG GBM pretreated for 3 hours with 10 μmol/L LY-2584702 and 10 μmol/L BMS-777607 vs. vehicle control at 60 and 300 minutes after addition of ¹³C-glucose (n = 4). Statistically significant (>1.5 fold) metabolites are highlighted. D, JHH136 spheres were treated with inhibitors (10 μmol/L each) for 72 hours for western blot analysis. LY-2584702, S6K1 inhibitor, reduces phosphorylation of rpS6 and CAD leading to sustained impairment of pyrimidine synthesis and cell growth. Treatment with BMS-777607 increases H2A.X phosphorylation at Serine 139, indicating an increase in double-stranded DNA breaks. E, Mayo59 spheres were treated as in D. S6K1 inhibition reduces phosphorylation of rpS6 and CAD, impairing pyrimidine synthesis. DNA damage is evident in combination S6K1 and AXL inhibition.

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Synoeca Septentrionalis

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PTEN Glioblastoma Pyrimidine P70-S6 Kinase 1 Biosynthesis Cancer research Chemistry Biology Biochemistry Gene Phosphorylation PI3K/AKT/mTOR pathway Signal transduction Protein kinase B

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Title: Figure 3 from Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma

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Publication year: 2024

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Authors: Catherine A. Behrmann, Kelli N. Ennis, P.N. Sarma, Collin Wetzel, Nicholas A. Clark, Kate M. Von Handorf, Subrahmanya Vallabhapurapu, Cristina Andreani, James Reigle, Pier Paolo Scaglioni, Jarek Meller, Maria Czyzyk-Krzeska, Ady Kendler, Xiaoyang Qi, Jann N. Sarkaria, Mario Medvedovic, Soma Sengupta, Biplab Dasgupta, David R. Plas

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Concepts: PTEN, Glioblastoma, Pyrimidine, P70-S6 Kinase 1, Biosynthesis, Cancer research, Chemistry, Biology, Biochemistry, Gene, Phosphorylation, PI3K/AKT/mTOR pathway, Signal transduction, Protein kinase B

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abstract_inverted_index.Serine	144
abstract_inverted_index.Steady	11
abstract_inverted_index.change	58
abstract_inverted_index.damage	173
abstract_inverted_index.siPTEN	20
abstract_inverted_index.breaks.	152
abstract_inverted_index.control	26, 81
abstract_inverted_index.evident	175
abstract_inverted_index.glucose	61
abstract_inverted_index.growth.	136
abstract_inverted_index.labeled	62
abstract_inverted_index.leading	127
abstract_inverted_index.minutes	86
abstract_inverted_index.reduces	121, 163
abstract_inverted_index.spheres	103, 155
abstract_inverted_index.treated	23, 105, 157
abstract_inverted_index.vehicle	25, 80
abstract_inverted_index.western	115
abstract_inverted_index.μmol/L	73, 77, 109
abstract_inverted_index.(>1.5	96
abstract_inverted_index.addition	88
abstract_inverted_index.increase	148
abstract_inverted_index.μmol/L)	32, 37
abstract_inverted_index.Treatment	137
abstract_inverted_index.abundance	14
abstract_inverted_index.analysis.	117
abstract_inverted_index.impairing	169
abstract_inverted_index.increases	140
abstract_inverted_index.precursor	51
abstract_inverted_index.sustained	129
abstract_inverted_index.synthesis	133
abstract_inverted_index.BMS-777607	78, 139
abstract_inverted_index.LY-2584702	74
abstract_inverted_index.counteract	4
abstract_inverted_index.impairment	130
abstract_inverted_index.indicating	146
abstract_inverted_index.inhibition	162
abstract_inverted_index.inhibitor,	120
abstract_inverted_index.inhibitors	3, 38, 107
abstract_inverted_index.metabolite	13
abstract_inverted_index.nucleotide	48
abstract_inverted_index.pretreated	67
abstract_inverted_index.pyrimidine	5, 132, 170
abstract_inverted_index.synthesis.	171
abstract_inverted_index.LY-2584702,	118
abstract_inverted_index.combination	28, 177
abstract_inverted_index.metabolites	52, 63, 98
abstract_inverted_index.significant	95
abstract_inverted_index.transfected	18
abstract_inverted_index.(BMS-777607,	35
abstract_inverted_index.(LY-2584702,	30
abstract_inverted_index.biosynthesis	6
abstract_inverted_index.highlighted.	100
abstract_inverted_index.<p>S6K1	0
abstract_inverted_index.Statistically	94
abstract_inverted_index.PTEN-deficient	8
abstract_inverted_index.double-stranded	150
abstract_inverted_index.phosphorylation	122, 142, 164
abstract_inverted_index.<b>A</b>.	54
abstract_inverted_index.<b>A,</b>	10
abstract_inverted_index.<b>B,</b>	45
abstract_inverted_index.<b>C,</b>	55
abstract_inverted_index.<b>D</b>.	160
abstract_inverted_index.<b>D,</b>	101
abstract_inverted_index.<b>E,</b>	153
abstract_inverted_index.(<i>n</i>	42, 91
abstract_inverted_index.inhibition.</p>	181
abstract_inverted_index.log<sub>2</sub>	56
abstract_inverted_index.[U]-<sup>13</sup>C	60
abstract_inverted_index.<sup>13</sup>C-glucose	90
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	19
citation_normalized_percentile.value	0.19506192
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False