A cell motility screen reveals role for MARCKS-related protein in adherens junction formation and tumorigenesis.

PloS One
Alexander E Finlayson, Kevin W Freeman

Abstract

Invasion through the extracellular matrix (ECM) is important for wound healing, immunological responses and metastasis. We established an invasion-based cell motility screen using Boyden chambers overlaid with Matrigel to select for pro-invasive genes. By this method we identified antisense to MARCKS related protein (MRP), whose family member MARCKS is a target of miR-21, a microRNA involved in tumor growth, invasion and metastasis in multiple human cancers. We confirmed that targeted knockdown of MRP, in both EpRas mammary epithelial cells and PC3 prostate cancer cells, promoted in vitro cell migration that was blocked by trifluoperazine. Additionally, we observed increased immunofluoresence of E-cadherin, beta-catenin and APC at sites of cell-cell contact in EpRas cells with MRP knockdown suggesting formation of adherens junctions. By wound healing assay we observed that reduced MRP supported collective cell migration, a type of cell movement where adherens junctions are maintained. However, destabilized adherens junctions, like those seen in EpRas cells, are frequently important for oncogenic signaling. Consequently, knockdown of MRP in EpRas caused loss of tumorigenesis in vivo, and reduced Wnt3a induced TCF reporter signal...Continue Reading

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Citations

Jul 10, 2012·Breast Cancer Research and Treatment·Kristin JonsdottirJan P A Baak
Apr 9, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lantu GouJinliang Yang
Sep 13, 2012·Molecular Reproduction and Development·Amanda L PattersonJason E Bruemmer
Mar 17, 2016·Drug Discovery Today·Milla KibbleTero Aittokallio
Sep 16, 2015·Chinese Journal of Cancer·Sha HeJian Zhang
Feb 12, 2015·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Denise NiewerthJacqueline Cloos
Feb 5, 2019·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Maayan LustigDafna Benayahu
May 24, 2018·Journal of Biomedical Science·Mohamed El AmriGerhard Schlosser
Jul 10, 2012·The Journal of Biological Chemistry·Hermann KalwaThomas Michel

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Methods Mentioned

BETA
myristoylation
transfection
PCR
scraping
PMA

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