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Updated: Aug 9, 2026
Transcriptomic Analysis of Human Retinal Surgical Specimens Using jouRNAl
Published on: August 14, 2013
Decryption of the retinoid death code in leukemia
Lucia Altucci1, Hinrich Gronemeyer
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, C U de Strasbourg, France. lucia.altucci@unina2.it
Abstract:
The recent elucidation of several molecular paradigms by which retinoids regulate growth, differentiation, and apoptosis highlights their promise as drugs for cancer therapy and prevention. Several novel signaling pathways by which retinoids induce cell death have been identified recently. They comprise (a) the induction by RARalpha-selective retinoids of the tumor-selective death ligand TRAIL that kills acute promyelocytic leukemia (APL) cells in a paracrine mode of action, which is the cause of retinoic acid-induced apoptosis after maturation: (b) a novel RARalpha-independent rexinoid-PKA cross-talk that induces maturation of both ATRA-sensitive and ATRA-resistant APL cells and does not invoke ligand-induced alteration of PML-RARalpha signaling, stability, or compartmentalization; and (c) a novel rexinoid signaling pathway that triggers apoptosis of immature APL cells and may correspond to a default death pathway that is operative in the absence of "survival" factors. This rexinoid apoptosis is inhibited by RXR but not RAR antagonists and is distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis. Here we discuss the promise of retinoids for cancer treatment and prevention with an emphasis on the recently identified mechanisms by which they control (cancer) cell proliferation.
Insights
Retinoids show promise for cancer therapy by inducing cancer cell death through novel pathways. These mechanisms involve tumor-selective ligands and distinct signaling routes, offering new avenues for treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Retinoids regulate crucial cellular processes including growth, differentiation, and apoptosis.
- Their potential as anticancer drugs for therapy and prevention is significant.
- Understanding retinoid signaling is key to developing new cancer treatments.
Purpose of the Study:
- To elucidate novel molecular mechanisms by which retinoids induce cancer cell death.
- To highlight the therapeutic promise of retinoids in cancer treatment and prevention.
- To emphasize recently identified pathways controlling cancer cell proliferation.
Main Methods:
- Identification of novel retinoid-induced signaling pathways.
- Analysis of retinoid effects on acute promyelocytic leukemia (APL) cells.
- Investigation of retinoic acid receptor (RAR) and retinoid X receptor (RXR) signaling.
Main Results:
- Retinoids induce tumor-selective death ligand TRAIL, causing paracrine apoptosis in APL cells.
- A novel RARalpha-independent cross-talk between rexinoids and PKA promotes APL cell maturation.
- A distinct rexinoid pathway triggers apoptosis in immature APL cells, independent of RAR agonists.
Conclusions:
- Retinoids offer promising therapeutic strategies for cancer through multiple cell death pathways.
- Novel RARalpha-independent and RXR-antagonized pathways contribute to retinoid's anticancer effects.
- Further research into these mechanisms can optimize retinoid-based cancer therapies.
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