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Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
- Source :
- iScience, Vol 24, Iss 12, Pp 103442- (2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Summary: Cancer stem cells (CSCs) are documented to play a key role in tumorigenesis and therapy resistance. Despite significant progress in clinical oncology, CSC reservoirs remain elusive and difficult to eliminate. Reverse-turn peptidomimetics were characterized as disruptors of CBP/beta-Catenin interactions and represent a promising avenue to curb hyperactive canonical Wnt/beta-Catenin signaling in CSCs. Recent studies suggested Sam68 as a critical mediator of reverse-turn peptidomimetics response in CSC populations. Using computational and biochemical approaches we confirmed Sam68 as a primary target of reverse-turn peptidomimetics. Furthermore, we executed an in silico drug discovery pipeline to identify yet uncharacterized reverse-turn peptidomimetic structures displaying superior anti-CSC activity in transformed pluripotent and colorectal cancer cell models. Thus, we identified YB-0158 as a reverse-turn peptidomimetic small molecule with enhanced translational potential, altering key hallmarks of human colorectal CSCs in patient-derived ex vivo organoids and in vivo serial tumor transplantation.
- Subjects :
- Pharmacology
Biochemistry
Stem cells research
Cancer
Science
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 24
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.4b364fa1b8740e1b8dceb3a7778dcb2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2021.103442