Oncogenic PKC-ι activates Vimentin during epithelial-mesenchymal transition in melanoma; a study based on PKC-ι and PKC-ζ specific inhibitors

Cell Adhesion & Migration
Wishrawana S RatnayakeMildred Acevedo-Duncan

Abstract

Melanoma is one of the fastest growing cancers in the United States and is accompanied with a poor prognosis owing to tumors being resistant to most therapies. Atypical protein kinase Cs (aPKC) are involved in malignancy in many cancers. We previously reported that aPKCs play a key role in melanoma's cell motility by regulating cell signaling pathways which induce epithelial-mesenchymal Transition (EMT). We tested three novel inhibitors; [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) which are specific to protein kinase C-iota (PKC-ι) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) which is specific to PKC-zeta (PKC-ζ) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes. Molecular modeling was used to identify potential binding sites for the inhibitors and to predict selectivity. Kinase assay showed >50% inhibition for specified targets beyond 5 μM for all inhibitors. Both ICA-1 and ζ-Stat significantly reduced cell proliferation and induced apoptosis, while ICA-1 als...Continue Reading

References

Jul 1, 1993·Genes & Development·M L ScottD Baltimore
Oct 31, 2006·Nature Cell Biology·Jong In YookStephen J Weiss
Jan 24, 2008·Cell Proliferation·R PatelM Acevedo-Duncan
Apr 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cecilia SahlgrenUrban Lendahl
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·W James Nelson
Feb 15, 2011·The International Journal of Biochemistry & Cell Biology·Prajit PillaiMildred Acevedo-Duncan
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Mar 14, 2013·Progress in Molecular Biology and Translational Science·Antonis KourtidisPanos Z Anastasiadis
Jul 25, 2013·Cell Adhesion & Migration·Adrian Gunaratne, Gianni M Di Guglielmo
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
Jun 26, 2014·Journal of Visualized Experiments : JoVE·Calvin R JustusLi V Yang
Jan 17, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Gang XiDavid R Clemmons
Apr 3, 2016·Cold Spring Harbor Protocols·Maria FeoktistovaMartin Leverkus

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Citations

Oct 16, 2019·Pharmaceutical Patent Analyst·Hermann Am Mucke

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Methods Mentioned

BETA
immunoprecipitation
PCR
reverse-immunoprecipitation
immunoprecipitations

Software Mentioned

Stat
ProteinSimple
1T
MODEL
AutoDockTools
ICA
AutoDock Vina
Linux
AlphaView
VassarStats

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