Deregulating cellular metabolism through non-genotoxic carcinogens (WP5571)

Homo sapiens

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Pathway representing the non-genotoxic induction, through doxycycline and FCCP, of the hallmark of cancer deregulating cellular metabolism. This pathway mainly focuses on the role of the mitochondria and it’s dysregulation.

For a description of pathway objects, see the WikiPathways Legend.

Authors

, Alex Pico , and Egon Willighagen

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

malignant cell

Pathway Ontology

cancer pathway

Disease Ontology

cancer

Participants
Query Drugst.One

Label Type Compact URI Comment
FCCP Metabolite chebi:75458
Doxycycline Metabolite hmdb:HMDB14399
leucine Metabolite chebi:25017
TSC1 GeneProduct ensembl:ENSG00000165699
EIF2A GeneProduct ensembl:ENSG00000144895
MYC GeneProduct ensembl:ENSG00000136997
OMA1 GeneProduct ensembl:ENSG00000162600
LONP2 GeneProduct ensembl:ENSG00000102910
CLPP GeneProduct ensembl:ENSG00000125656
SESN2 GeneProduct ensembl:ENSG00000130766
GDF15 GeneProduct ensembl:ENSG00000130513
HSPD1 GeneProduct ensembl:ENSG00000144381
LARS1 GeneProduct ensembl:ENSG00000133706
LONP1 GeneProduct ensembl:ENSG00000196365
LAT1 GeneProduct ensembl:ENSG00000155465
AKT1 GeneProduct ensembl:ENSG00000142208
MTORC1 GeneProduct ensembl:ENSG00000198793
mTORC2 GeneProduct ensembl:ENSG00000198793
MARS1 GeneProduct ensembl:ENSG00000166986
PHB2 GeneProduct ensembl:ENSG00000215021
ATF4 GeneProduct ensembl:ENSG00000128272
TRAP1 GeneProduct ensembl:ENSG00000126602
PHB1 GeneProduct ensembl:ENSG00000167085
IRS1 GeneProduct ensembl:ENSG00000169047
FOXO1 GeneProduct ensembl:ENSG00000150907
TSC2 GeneProduct ensembl:ENSG00000103197
AMPK Protein eccode:2.7.11.1
Class IIa HDACs Protein eccode:3.5.1.98
PI3K Protein interpro:IPR000403

References

  1. Effect of phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 on the function of reversing factor in the initiation of protein synthesis. Matts RL, Levin DH, London IM. Proc Natl Acad Sci U S A. 1983 May;80(9):2559–63. PubMed Europe PMC Scholia
  2. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Science. 2005 Feb 18;307(5712):1098–101. PubMed Europe PMC Scholia
  3. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Magnuson B, Ekim B, Fingar DC. Biochem J. 2012 Jan 1;441(1):1–21. PubMed Europe PMC Scholia
  4. mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc. Masui K, Tanaka K, Akhavan D, Babic I, Gini B, Matsutani T, et al. Cell Metab. 2013 Nov 5;18(5):726–39. PubMed Europe PMC Scholia
  5. Sestrin2 is a leucine sensor for the mTORC1 pathway. Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, et al. Science. 2016 Jan 1;351(6268):43–8. PubMed Europe PMC Scholia
  6. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, et al. Science. 2016 Jan 1;351(6268):53–8. PubMed Europe PMC Scholia
  7. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. Quirós PM, Prado MA, Zamboni N, D’Amico D, Williams RW, Finley D, et al. J Cell Biol. 2017 Jul 3;216(7):2027–45. PubMed Europe PMC Scholia
  8. The Akt pathway in oncology therapy and beyond (Review). Nitulescu GM, Van De Venter M, Nitulescu G, Ungurianu A, Juzenas P, Peng Q, et al. Int J Oncol. 2018 Dec;53(6):2319–31. PubMed Europe PMC Scholia
  9. The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation. Kowalsky AH, Namkoong S, Mettetal E, Park HW, Kazyken D, Fingar DC, et al. J Biol Chem. 2020 Feb 14;295(7):1769–80. PubMed Europe PMC Scholia
  10. ATF4-Dependent NRF2 Transcriptional Regulation Promotes Antioxidant Protection during Endoplasmic Reticulum Stress. Sarcinelli C, Dragic H, Piecyk M, Barbet V, Duret C, Barthelaix A, et al. Cancers (Basel). 2020 Mar 1;12(3):569. PubMed Europe PMC Scholia
  11. mTOR-Dependent Role of Sestrin2 in Regulating Tumor Progression of Human Endometrial Cancer. Shin J, Bae J, Park S, Kang HG, Shin SM, Won G, et al. Cancers (Basel). 2020 Sep 4;12(9):2515. PubMed Europe PMC Scholia
  12. Non-genomic activation of the AKT-mTOR pathway by the mitochondrial stress response in thyroid cancer. Doolittle WKL, Park S, Lee SG, Jeong S, Lee G, Ryu D, et al. Oncogene. 2022 Oct;41(44):4893–904. PubMed Europe PMC Scholia