The interactome and spatial redistribution feature of Ca2+ receptor protein calmodulin reveals a novel role in invadopodia-mediated invasion

Cell Death & Disease
Tao LiXuejun Yang

Abstract

Numerous studies have shown that calmodulin (CaM) is a major regulator of calcium-dependent signaling, which regulates cell proliferation, programmed cell death, and autophagy in cancer. However, limited information is available on mechanisms underlying the effect of CaM on the invasive property of glioblastoma multiforme (GBM) cells, especially with respect to invadopodia formation. In this study, we find that CaM serves as a prognostic factor for GBM, and it is strongly associated with the invasive nature of this tumor. Results of preliminary experiments indicated that CaM concentration was significantly correlated with the invasive capacity of and invadopodia formation by different GBM cell lines. CaM inhibition via a small hairpin RNA or a pharmacological inhibitor significantly disrupted invadopodia formation and MMP activity and downregulated vimentin expression. Moreover, CaM knockdown exerted a strong anti-invasive effect on GBM in vivo. Interestingly, epidermal growth factor treatment promoted CaM redistribution from the nucleus to the cytoplasm, eventually activating invadopodia-associated proteins by binding to them via their cytosolic-binding sites. Moreover, CaM inhibition suppressed the activation of invadopodia-a...Continue Reading

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Citations

Jan 30, 2020·International Journal of Molecular Sciences·Antonio Villalobo, Martin W Berchtold
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Ilenia MasiLaura Rosanò
Dec 20, 2020·Cancer Treatment and Research Communications·Mohammed A AzabAhmed Y Azzam
Jul 3, 2021·Disease Markers·Jin-Zhang SunXue-Jun Yang
Jun 22, 2021·Frontiers in Cellular Neuroscience·Jae-Seon SoKyung-Seok Han
May 25, 2021·Journal of the Chinese Medical Association : JCMA·Xian LiuLiang-Ting Lin

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Methods Mentioned

BETA
surgical resection
co-immunoprecipitation assay
co-immunoprecipitation
zymography
xenograft
protein assay
electrophoresis
transfection

Software Mentioned

ImageJ
STRING
SPSS
Cytoscape

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