Pharmacological targeting of Sam68 functions in colorectal cancer stem cells

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...

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Autores principales:	Angelique N. Masibag, Christopher J. Bergin, Joshua R. Haebe, Aïcha Zouggar, Muhammad S. Shah, Tamara Sandouka, Amanda Mendes da Silva, François M. Desrochers, Aube Fournier-Morin, Yannick D. Benoit
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Pharmacology Biochemistry Stem cells research Cancer Science Q
Acceso en línea:	https://doaj.org/article/a4b364fa1b8740e1b8dceb3a7778dcb2
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spelling	oai:doaj.org-article:a4b364fa1b8740e1b8dceb3a7778dcb22021-11-28T04:36:27ZPharmacological targeting of Sam68 functions in colorectal cancer stem cells2589-004210.1016/j.isci.2021.103442https://doaj.org/article/a4b364fa1b8740e1b8dceb3a7778dcb22021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014139https://doaj.org/toc/2589-0042Summary: 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.Angelique N. MasibagChristopher J. BerginJoshua R. HaebeAïcha ZouggarMuhammad S. ShahTamara SandoukaAmanda Mendes da SilvaFrançois M. DesrochersAube Fournier-MorinYannick D. BenoitElsevierarticlePharmacologyBiochemistryStem cells researchCancerScienceQENiScience, Vol 24, Iss 12, Pp 103442- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pharmacology Biochemistry Stem cells research Cancer Science Q
spellingShingle	Pharmacology Biochemistry Stem cells research Cancer Science Q Angelique N. Masibag Christopher J. Bergin Joshua R. Haebe Aïcha Zouggar Muhammad S. Shah Tamara Sandouka Amanda Mendes da Silva François M. Desrochers Aube Fournier-Morin Yannick D. Benoit Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
description	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.
format	article
author	Angelique N. Masibag Christopher J. Bergin Joshua R. Haebe Aïcha Zouggar Muhammad S. Shah Tamara Sandouka Amanda Mendes da Silva François M. Desrochers Aube Fournier-Morin Yannick D. Benoit
author_facet	Angelique N. Masibag Christopher J. Bergin Joshua R. Haebe Aïcha Zouggar Muhammad S. Shah Tamara Sandouka Amanda Mendes da Silva François M. Desrochers Aube Fournier-Morin Yannick D. Benoit
author_sort	Angelique N. Masibag
title	Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
title_short	Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
title_full	Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
title_fullStr	Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
title_full_unstemmed	Pharmacological targeting of Sam68 functions in colorectal cancer stem cells
title_sort	pharmacological targeting of sam68 functions in colorectal cancer stem cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a4b364fa1b8740e1b8dceb3a7778dcb2
work_keys_str_mv	AT angeliquenmasibag pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT christopherjbergin pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT joshuarhaebe pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT aichazouggar pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT muhammadsshah pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT tamarasandouka pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT amandamendesdasilva pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT francoismdesrochers pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT aubefourniermorin pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells AT yannickdbenoit pharmacologicaltargetingofsam68functionsincolorectalcancerstemcells
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Pharmacological targeting of Sam68 functions in colorectal cancer stem cells

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