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Dr. Raphaël Rodriguez - An iron hand over cancer stem cells

R. Rodriguez.jpg

Prestige seminar

Raphaël Rodriguez

Institut Curie, Paris

An iron hand over cancer stem cells

Cancer stem cells (CSCs) have been shown to be refractory to conventional therapeutic agents, can promote metastasis, and have been linked to cancer relapse. Salinomycin can selectively kill CSCs. We have shown that salinomycin derivatives accumulate in lysosomes and sequester iron in this organelle. Accumulation of iron leads to the production of reactive oxygen species and lysosomal membrane permeabilization, which in turn promotes cell death by ferroptosis. These findings have revealed the prevalence of iron homeostasis in CSCs and paved the way toward the development of next-generation therapeutics. The role of iron in the maintenance of cancer stem cells will be discussed.

Selected references

  • Mai TT, Hamaï A, Hienzsch A, Cañeque T, Müller S, Wicinski J, Cabaud O, Leroy C, David A, Acevedo V, Ryo A, Ginestier C, Birnbaum D, Charafe-Jauffret E, Codogno P, Mehrpour M, Rodriguez R. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem 2017 9(10):1025-1033
  • Cañeque T, Müller S, Rodriguez R. Visualizing biologically active small molecules in cells using click chemistry. Nat Rev Chem 2018 2: 202–215
  • Tyler DS, Vappiani J, Cañeque T, Lam EYN, Ward A, Gilan O, Chan YC, Hienzsch A, Rutkowska A, Werner T, Wagner AJ, Lugo D, Gregory R, Ramirez Molina C, Garton N, Wellaway CR, Jackson S, MacPherson L, Figueiredo M, Stolzenburg S, Bell CC, House C, Dawson SJ, Hawkins ED, Drewes G, Prinjha RK, Rodriguez R, Grandi P, Dawson MA. Click chemistry enables preclinical evaluation of targeted epigenetic therapies. Science. 2017 356(6345):1397-1401
  • Zacharioudakis E, Agarwal P, Bartoli A, Abell N, Kunalingam L, Bergoglio V, Xhemalce B, Miller KM, Rodriguez R. Chromatin Regulates Genome Targeting with Cisplatin. Angew Chem Int Ed Engl 2017 56(23):6483-6487
  • Abell NS, Mercado M, Cañeque T, Rodriguez R, Xhemalce B. Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells. J Am Chem Soc 2017 139(4):1400-1403
  • Cañeque T, Gomes F, Mai TT, Maestri G, Malacria M, Rodriguez R. Synthesis of marmycin A and investigation into its cellular activity. Nat Chem 2015 7(9):744-51
  • Rodriguez R, Miller KM. Unravelling the genomic targets of small molecules using high-throughput sequencing. Nat Rev Genet 2014 15(12):783-96
  • Larrieu D, Britton S, Demir M, Rodriguez R, Jackson SP. Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science 2014 344(6183):527-3

 

Contact: Sébastien Britton (sebastien.britton@ipbs.fr)

Note for visitors: Please come with a valid identity card

 

13 Dec

11:00 - 12:00

Seminar room - IPBS - Campus 205