Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration - HAL Accéder directement au contenu
Article dans une revue International Journal of Molecular Sciences Année : 2023

Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration

Ali Dayoub
  • Fonction : Auteur
Artem Fokin
  • Fonction : Auteur
Maria Lomakina
  • Fonction : Auteur
John James
  • Fonction : Auteur
Marina Plays
  • Fonction : Auteur
Tom Jacquin
Nikita Novikov
  • Fonction : Auteur
Rostislav Vorobyov
Anastasia Schegoleva
  • Fonction : Auteur
Karina Rysenkova
Julia Gaboriaud
  • Fonction : Auteur
Sergey Leonov
Evgeny Denisov
Alexis Gautreau
Antonina Alexandrova
  • Fonction : Auteur

Résumé

Whole exome sequencing of invasive mammary carcinomas revealed the association of mutations in PTEN and ZFHX3 tumor suppressor genes (TSGs). We generated single and combined PTEN and ZFHX3 knock-outs (KOs) in the immortalized mammary epithelial cell line MCF10A to study the role of these genes and their potential synergy in migration regulation. Inactivation of PTEN, but not ZFHX3, induced the formation of large colonies in soft agar. ZFHX3 inactivation in PTEN KO, however, increased colony numbers and normalized their size. Cell migration was affected in different ways upon PTEN and ZFHX3 KO. Inactivation of PTEN enhanced coordinated cell motility and thus, the collective migration of epithelial islets and wound healing. In contrast, ZFHX3 knockout resulted in the acquisition of uncoordinated cell movement associated with the appearance of immature adhesive junctions (AJs) and the increased expression of the mesenchymal marker vimentin. Inactivation of the two TSGs thus induces different stages of partial epithelial-to-mesenchymal transitions (EMT). Upon double KO (DKO), cells displayed still another motile state, characterized by a decreased coordination in collective migration and high levels of vimentin but a restoration of mature linear AJs. This study illustrates the plasticity of migration modes of mammary cells transformed by a combination of cancer-associated genes.
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Dates et versions

hal-04263700, version 1 (29-10-2023)

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Ali Dayoub, Artem Fokin, Maria Lomakina, John James, Marina Plays, et al.. Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration. International Journal of Molecular Sciences, 2023, 24 (1), pp.313. ⟨10.3390/ijms24010313⟩. ⟨hal-04263700⟩

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