CBP501 inhibits EGF-dependent cell migration, invasion and epithelial-to-mesenchymal transition of non-small cell lung cancer cells by blocking KRas to calmodulin binding

Oncotarget
Naoya SaitoTakumi Kawabe

Abstract

The anti-cancer agent CBP501 binds to calmodulin (CaM). Recent studies showed that migration and metastasis are inhibited by several CaM antagonists. However, there is no available evidence that CBP501 has similar effects. Here we found that CBP501 inhibits migration of non-small cell lung cancer (NSCLC) cells in vitro, even in the presence of migration inducing factors such as WNT, IL-6, and several growth factors. CBP501 also inhibited epidermal growth factor (EGF) enhanced invasion and the epithelial-to-mesenchymal transition (EMT), and this inhibition was accompanied by (i) suppression of Akt and ERK1/2 phosphorylation, and (ii) suppression of expression of transcription factor Zeb1 and the mesenchymal marker Vimentin. A pull down analysis performed using sepharose-immobilized CaM showed that CBP501 blocks the interaction between CaM and KRas. Furthermore, EGF induced Akt activation and cell migration was effectively suppressed by KRas down-regulation in NSCLC cells. Stable knockdown of KRas also made cells insensitive to CBP501's inhibition of growth factor-induced migration. Taken together, these results indicate that CBP501 inhibits binding of CaM with KRas and thereby suppresses the PI3K/AKT pathway, migration, invasion...Continue Reading

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Citations

Aug 18, 2020·Journal of Biomolecular NMR·Christopher B MarshallMitsuhiko Ikura
Jan 30, 2020·International Journal of Molecular Sciences·Antonio Villalobo, Martin W Berchtold
Apr 3, 2020·Science Signaling·Benjamin M M GrantChristopher B Marshall
Apr 25, 2020·International Journal of Molecular Sciences·Benjamin M M GrantChristopher B Marshall
Feb 18, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yaozhen PanChungen Xing
Jan 28, 2022·Expert Opinion on Drug Discovery·Kashif HaiderAhmed Kamal

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Methods Mentioned

BETA
pull down
GTPases
pull-down
Assay
electrophoresis

Software Mentioned

Image

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