Indacaterol inhibits collective cell migration and IGDQ-mediated single cell migration in metastatic breast cancer MDA-MB-231 cells

Sophie Ayama-Canden, Rodolfo Tondo, Martha Liliana Pineros Leyton, Noëlle Ninane, Catherine Demazy, Marc Dieu, Antoine Fattaccioli, Aude Sauvage, Tijani Tabarrant, Stéphane Lucas, Davide Bonifazi, Carine Michiels

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Abstract

Metastasis is the main cause of deaths related to breast cancer. This is particular the case for triple negative breast cancer. No targeted therapies are reported as efficient until now. The extracellular matrix, in particular the fibronectin type I motif IGDQ, plays a major role in regulating cell migration prior metastasis formation. This motif interacts with specific integrins inducing their activation and the migratory signal transduction.Here, we characterized the migratory phenotype of MDA-MB-231 cells, using functionalized IGDQ-exposing surfaces, and compared it to integrin A5 and integrin B3 knock-down cells. A multiomic analysis was developed that highlighted the splicing factor SRSF6 as a putative master regulator of cell migration and of integrin intracellular trafficking. Indacaterol-induced inhibition of SRSF6 provoked: i) the inhibition of collective and IGDQ-mediated cell migration and ii) ITGA5 sequestration into endosomes and lysosomes. Upon further studies, indacaterol may be a potential therapy to prevent cell migration and reduce metastasis formation in breast cancer. [MediaObject not available: see fulltext.]

Original languageEnglish
Article number301
Pages (from-to)301
Number of pages20
JournalCell communication and signaling
Volume21
Issue number1
DOIs
Publication statusPublished - Dec 2023

Keywords

  • Humans
  • Female
  • Breast Neoplasms/pathology
  • MDA-MB-231 Cells
  • Integrins/metabolism
  • Cell Movement
  • Triple Negative Breast Neoplasms
  • Cell Line, Tumor
  • Cell Adhesion
  • Serine-Arginine Splicing Factors
  • Phosphoproteins/metabolism
  • Motogenic
  • Integrin alpha 5
  • Breast cancer
  • Indacaterol
  • Metastasis
  • IGDQ motogenic motif
  • Fibronectin type I
  • Integrin beta 3
  • SRFS6
  • Cell migration

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