TGFbeta induces an atypical EMT to evade immune mechanosurveillance in lung adenocarcinoma dormant metastasis
Menée à l'aide de lignées cellulaires et de modèles murins, cette étude met en évidence un mécanisme par lequel le facteur de croissance TGFbêta favorise l'échappement immunitaire des métastases dormantes des adénocarcinomes pulmonaires primitifs en induisant une transition épithélio-mésenchymateuse atypique qui réduit la rigidité biomécanique des cellules progénitrices métastatiques et les protège des lymphocytes cytotoxiques
Different forms of epithelial-to-mesenchymal transition (EMT) manifest during tumor progression. Little is known about the mechanistic basis and functional role of these distinct EMTs. We explored this question in lung adenocarcinoma (LUAD) primitive progenitors, which are competent to enter dormancy in response to transforming growth factor-
β (TGFβ) upon metastatic dissemination. The TGFβ response in these cells includes growth arrest and a full EMT that subsequently transitions into an atypical mesenchymal state of round morphology and lacking actin stress fibers. TGFβ drives this transition by inducing expression of the actin depolymerizing protein gelsolin, which converts a migratory, stress-fiber-rich phenotype into a cortical actin-rich, spheroidal state. This transition lowers the biomechanical stiffness of metastatic progenitors and protects them from killing by cytotoxic lymphocytes. Gelsolin-deficient LUAD progenitors can enter dormancy but succumb to immune surveillance. Thus, quiescent LUAD metastatic progenitors undergo an atypical EMT to avert immune surveillance during TGFβ-driven metastatic dormancy.
Nature Cancer , article en libre accès, 2026