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Video Abstract (AI generated) (01:29) Paper Preprint eLifeCARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73-associated reduction of invasiveness act via altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 and CARM1 knockout alter the epigenetic plasticity with remarkable difference, arguing distinct modes of action between the small-molecule and genetic perturbation. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process.
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Fengling Li. (2021, Sep 30).A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion[Video]. Scitok. https://scitok.com/project/p/32581234
Cai Xiao-Chuan. "A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion" Scitok, uploaded by Li Fengling, 30 Sep, 2021, https://scitok.com/project/p32581234
Fengling Li. "A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion" Scitok. (Sep 30, 2021). https://scitok.com/project/p/32581234
Fengling Li (Sep 30, 2021). A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion Scitok. https://scitok.com/project/p/32581234
Fengling Li. A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion[video]. 2021 Sep 30. https://scitok.com/project/p/32581234
@online{al2006link, title={ A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion }, author={ Li, Fengling }, organization={Scitok}, month={ Sep }, day={ 30 }, year={ 2021 }, url = {https://scitok.com/project/p/32581234}, }