ArticleMolecular and cellular biology2008
Thalidomide induces limb anomalies by PTEN stabilization, Akt suppression, and stimulation of caspase-dependent cell death.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 72 citations in OpenAlex.
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- A New Strategy for the Old Challenge of Thalidomide: Systems Biology Prioritization of Potential Immunomodulatory Drug (IMiD)-Targeted Transcription Factors.International journal of molecular sciences · 2023Article
- Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.Frontiers in cell and developmental biology · 2023Review
- Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action.British journal of clinical pharmacology · 2021Article
- Downregulation of long non-coding RNA MR4435-2HG suppresses breast cancer progression via the Wnt/β-catenin signaling pathway.Oncology letters · 2021Article
- Do Wortmannin and Thalidomide induce apoptosis by autophagy inhibition in 4T1 breast cancer cells in vitro and in vivo?American journal of translational research · 2021Article
- P63 modulates the expression of the WDFY2 gene which is implicated in cancer regulation and limb development.Bioscience reports · 2019Article
- High-throughput transcriptome analysis reveals that the loss of Pten activates a novel NKX6-1/RASGRP1 regulatory module to rescue microphthalmia caused by Fgfr2-deficient lenses.Human genetics · 2019Article
- A new target for thalidomide.Nature chemical biology · 2018Article
- Vertebrate embryos as tools for anti-angiogenic drug screening and function.Reproductive toxicology (Elmsford, N.Y.) · 2017Review
- Olfactory Receptors Modulate Physiological Processes in Human Airway Smooth Muscle Cells.Frontiers in physiology · 2016Article
- Thalidomide-induced teratogenesis: history and mechanisms.Birth defects research. Part C, Embryo today : reviews · 2015Review
- Inhibition of endothelial Slit2/Robo1 signaling by thalidomide restrains angiogenesis by blocking the PI3K/Akt pathway.Digestive diseases and sciences · 2014Article
- Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma.Acta biochimica et biophysica Sinica · 2014Review
- Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy.Oncogene · 2013Review
- Conserved nonsense-prone CpG sites in apoptosis-regulatory genes: conditional stop signs on the road to cell death.Evolutionary bioinformatics online · 2013Article
- A transgenic, mesodermal specific, Dkk1 mouse model recapitulates a spectrum of human congenital limb reduction defects.Differentiation; research in biological diversity · 2012Article
- Article
- Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells.PloS one · 2012Article
- Teratogenic effects of thalidomide: molecular mechanisms.Cellular and molecular life sciences : CMLS · 2011Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (Bmps) protects active PTEN from proteasomal degradation, resulting in suppression of Akt signaling. As a consequence, caspase-dependent cell death is stimulated by the intrinsic and Fas death receptor apoptotic pathway. Most importantly, thalidomide-induced limb deformities and microphthalmia in chicken embryos could be rescued by a pharmacological PTEN inhibitor as well as by insulin, a stimulant of Akt signaling. We therefore conclude that perturbation of PTEN/Akt signaling and stimulation of caspase activity is central to the teratogenic effects of thalidomide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.