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View article: ATR promotes mTORC1 activity via de novo cholesterol synthesis
ATR promotes mTORC1 activity via de novo cholesterol synthesis Open
DNA damage and cellular metabolism exhibit a complex interplay characterized by bidirectional feedback. Key mediators of these pathways include ATR and mTORC1, respectively. Previous studies established ATR as a regulatory upstream factor …
View article: Zinc availability in the tumor microenvironment dictates anti-PD1 response in <i>CDKN2A</i> <sup>Low</sup> tumors via increased macrophage phagocytosis
Zinc availability in the tumor microenvironment dictates anti-PD1 response in <i>CDKN2A</i> <sup>Low</sup> tumors via increased macrophage phagocytosis Open
Anti-PD1 therapies are primarily thought to rely on functional T cell responses; yet tumors with limited T cell infiltration can still benefit, suggesting alternative mechanisms contribute to therapeutic efficacy. Indeed, we found that mye…
View article: Table S8 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S8 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
TCGA melanoma patient data
View article: Data from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Data from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in approximately 50% of all human cancers. In its canonical role, p16 inhibits the G1–S-phase cell cycle progression through suppression of cyclin-dependent kina…
View article: Table S1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
CRISPR KO library containing 128 genes comprising the nucleotide metabolism signature
View article: Table S2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Primers used in this study
View article: Table S1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
CRISPR KO library containing 128 genes comprising the nucleotide metabolism signature
View article: FIGURE 2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
p16/CDKN2A negatively correlates with multiple nucleotide metabolism genes, proteins, and metabolites. A–D, SKMEL28 human melanoma cells were infected with lentivirus expressing a shRNA targeting p16 (shp16). shGFP was used as a control (s…
View article: FIGURE 1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Multiple CRISPR KO screens identify nucleotide metabolism genes that are selectively depleted in p16/CDKN2Alow cells. A, Schematic of our CRISPR screens. p16/Cdkn2a wildtype cells were infected with lentiviruses expressing shGFP control (s…
View article: Data from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Data from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in approximately 50% of all human cancers. In its canonical role, p16 inhibits the G1–S-phase cell cycle progression through suppression of cyclin-dependent kina…
View article: Table S6 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S6 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
mRNA expression of nucleotide metabolism genes
View article: Figure S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Figure S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
shp16 tumor bearing mice treated with methotrexate have a trend towards a survival advantage; and methotrexate does not affect body weight or blood cell counts. Related to Figure 5.
View article: FIGURE 5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
shp16 tumors are more sensitive to the antifolate methotrexate. A and B, SKMEL28 human melanoma cells were infected with lentivirus expressing a shRNA targeting GFP (shCont) or p16 (shp16). A total of 107 cells were subcutaneously implante…
View article: FIGURE 4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Multiple antifolates induce apoptosis in p16 knockdown cells. A–D, SKMEL28 human melanoma cells were infected with lentivirus expressing a shRNA targeting p16 (shp16). shGFP was used as a control (shCont). A, Cells were treated with the in…
View article: Figure S2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Figure S2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Knockdown or knockout of Cdkn2a in mouse melanoma cell lines increases sensitivity to multiple anti-folates but not to de novo pyrimidine synthesis; Knockdown of RB1 does not recapitulate the anti-folate response exhibited by shp16 cells. …
View article: Table S6 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S6 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
mRNA expression of nucleotide metabolism genes
View article: FIGURE 3 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 3 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
p16/CDKN2Alow cells are more sensitive to inhibitors of nucleotide metabolism. A, Table of inhibitors used in in vitro cell line studies. 1C metabolism = one carbon metabolism. B, SKMEL28 human melanoma cells were infected with lentivirus …
View article: FIGURE 1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Multiple CRISPR KO screens identify nucleotide metabolism genes that are selectively depleted in p16/CDKN2Alow cells. A, Schematic of our CRISPR screens. p16/Cdkn2a wildtype cells were infected with lentiviruses expressing shGFP control (s…
View article: Figure S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Figure S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
shp16 tumor bearing mice treated with methotrexate have a trend towards a survival advantage; and methotrexate does not affect body weight or blood cell counts. Related to Figure 5.
View article: Table S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
CRISPR screen results for mouse Yumm5.2 cells
View article: Table S3 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S3 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
CRISPR screen results for human SKMEL28 cells
View article: Table S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S4 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
CRISPR screen results for mouse Yumm5.2 cells
View article: Figure S1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Figure S1 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Knockdown of p16 or Cdkn2a in human and mouse melanoma cell lines, respectively, and DepMap dependency score data based on CDKN2A expression. Related to Figure 1.
View article: FIGURE 5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
shp16 tumors are more sensitive to the antifolate methotrexate. A and B, SKMEL28 human melanoma cells were infected with lentivirus expressing a shRNA targeting GFP (shCont) or p16 (shp16). A total of 107 cells were subcutaneously implante…
View article: Table S5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
31 common genes identified in screens and publicly available data
View article: FIGURE 6 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
FIGURE 6 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
De novo purine synthesis and one carbon metabolism genes are associated with worse overall survival in metastatic melanomas. Data from TCGA Skin Cutaneous Melanoma PanCancer Atlas (367 metastatic melanomas). Raw data can be found in Supple…
View article: Table S7 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S7 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Poly-Seq data of nucleotide metabolism genes
View article: Table S5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Table S5 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
31 common genes identified in screens and publicly available data
View article: Figure S2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Figure S2 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Knockdown or knockout of Cdkn2a in mouse melanoma cell lines increases sensitivity to multiple anti-folates but not to de novo pyrimidine synthesis; Knockdown of RB1 does not recapitulate the anti-folate response exhibited by shp16 cells. …
View article: Figure S3 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression
Figure S3 from <i>De Novo</i> Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression Open
Anti-folates induce death and increased DNA damage foci in shCdkn2a cells; shp16 cells do not mount a robust senescence-associated secretory phenotype (SASP) in response to Palbociclib; anti-proliferative effects of anti-folates are longer…