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bioRxiv · 10.1101/2020.10.09.332783

E-cadherin: Unexpected actor of invadopodia formation in pancreatic cancer

Dobric, A.·Germain, S.·Bonier, R.·Silvy, F.·Audebert, S.·Camoin, L.·Dusetti, N. J.·Soubeyran, P.·Iovanna, J.·Rigot, V.·Andre, F.
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Abstract

Graphical abstract BackgroundThe appearance of hybrid epithelial-mesenchymal (E/M) cells expressing E-cadherin is favourable for the establishment of pro-invasive function. However, the molecular mechanism and potential roles of E-cadherin in cancer cell invasion stay unexplored. MethodsWe used models of E/M hybrid cell lines, tissues sections and patient-derived xenografts from a multi-center clinical trial. E-cadherin involvement in invadopodia formation was assessed using a gelatin-FITC degradation assay. Mechanistic studies were performed by using proteomic analysis, siRNA strategy and proximity ligation assay. ResultsWe showed that E-cadherin is a critical component of invadopodia. This unexpected localization results from a synergistic trafficking of E-cadherin and MT1-MMP through Rab vesicle-dependent pathway. Modulation of E-cadherin expression or activation impacted invadopodia formation. Moreover, colocalization of E-cadherin and Actin in [-]ring structures|| as precursor of invadopodia reveals that E-cadherin is required for invadopodia structuration. ConclusionE-cadherin, initially localized in the adherens junctions could be recycled to nascent invadopodia where it will interact with several components such as Arp2/3, Cortactin or MT1-MMP. The trans-adhesive properties of E-cadherin are therefore essential for structuring invadopodia. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/332783v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@13b08e8org.highwire.dtl.DTLVardef@c5d19eorg.highwire.dtl.DTLVardef@14511cforg.highwire.dtl.DTLVardef@19436eb_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Dobric, A., Germain, S., Bonier, R., Silvy, F., Audebert, S., Camoin, L., Dusetti, N. J., Soubeyran, P., Iovanna, J., Rigot, V., Andre, F.. 2020-10-09. E-cadherin: Unexpected actor of invadopodia formation in pancreatic cancer. https://doi.org/10.1101/2020.10.09.332783

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