title: EMMPRIN regulates β1 integrin-mediated adhesion through Kindlin-3 in human melanoma cells.
abstract: EMMPRIN is known to promote tumor invasion through extracellular matrix (ECM) degradation. Here we report that EMMPRIN can regulate melanoma cell adhesion to the ECM through an interaction with β1 integrin involving kindlin-3. In this study, EMMPRIN knockdown in the human melanoma cell line M10 using siRNA decreased cell invasion and significantly increased cell adhesion and spreading. A morphological change from a round to a spread shape was observed associated with enhanced phalloidin-labelled actin staining. In situ proximity ligation assay and co-immunoprecipitation revealed that EMMPRIN silencing increased the interaction of β1 integrin with kindlin-3, a focal adhesion protein. This was associated with an increase in β1 integrin activation and a decrease in the phosphorylation of the downstream integrin kinase FAK. Moreover, the expression at both the transcript and protein level of kindlin-3 and of β1 integrin was inversely regulated by EMMPRIN. EMMPRIN did not regulate either talin expression or its interaction with β1 integrin. These results are consistent with our in vivo demonstration that EMMPRIN inhibition increased β1 integrin activation and its interaction with kindlin-3. To conclude, these findings reveal a new role of EMMPRIN in tumor cell migration through ß1 integrin/kindlin-3-mediated adhesion pathway.
authors: INSERM UMR-S 976, Paris, France.|Département de Dermatologie, AP-HP, Hôpital Saint-Louis, Paris, France.
authors: Julie
authors: J
authors: Delyon
authors: INSERM UMR-S 976, Paris, France.
authors: Farah
authors: F
authors: Khayati
authors: INSERM UMR-S 976, Paris, France.|Institute of Hematology (IUH), Université Paris-Diderot, Sorbonne Paris Cité, France.
authors: Ibtissem
authors: I
authors: Djaafri
authors: Laboratoire de Pharmacologie Biologique, AP-HP, Hôpital Saint-Louis, Paris, France.
authors: Marie-Pierre
authors: MP
authors: Podgorniak
authors: Laboratoire de Pharmacologie Biologique, AP-HP, Hôpital Saint-Louis, Paris, France.
authors: Aurélie
authors: A
authors: Sadoux
authors: Institute of Hematology (IUH), Université Paris-Diderot, Sorbonne Paris Cité, France.
authors: Niclas
authors: N
authors: Setterblad
authors: INSERM UMR-S 976, Paris, France.
authors: Zineb
authors: Z
authors: Boutalbi
authors: Neurobiologie intégrative des systémes cholinergiques CNRS UMR 3571-Département de Neuroscience- Institut Pasteur-25, rue du Dr Roux- 75724, Paris, Cedex 15, France.
authors: Kamel
authors: K
authors: Maouche
authors: Neurobiologie intégrative des systémes cholinergiques CNRS UMR 3571-Département de Neuroscience- Institut Pasteur-25, rue du Dr Roux- 75724, Paris, Cedex 15, France.
authors: Uwe
authors: U
authors: Maskos
authors: Université Paris Est Créteil, CNRS-UMR 7149, Créteil, France.
authors: Suzanne
authors: S
authors: Menashi
authors: INSERM UMR-S 976, Paris, France.|Département de Dermatologie, AP-HP, Hôpital Saint-Louis, Paris, France.|Institute of Hematology (IUH), Université Paris-Diderot, Sorbonne Paris Cité, France.
authors: Céleste
authors: C
authors: Lebbé
authors: INSERM UMR-S 976, Paris, France.|Institute of Hematology (IUH), Université Paris-Diderot, Sorbonne Paris Cité, France.|Laboratoire de Pharmacologie Biologique, AP-HP, Hôpital Saint-Louis, Paris, France.
authors: Samia
authors: S
authors: Mourah
mesh_terms: D000818:Animals; D051926:Basigin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000502:physiology*; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000473:pathology* / Q000503:physiopathology
chemical_list: C497886:BSG protein, human; C477322:FERMT3 protein, human; D019012:Integrin beta1; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D051926:Basigin
keywords: EMMPRIN; Kindlin-3; cell adhesion; melanoma; β1 integrin