Tumor-associated macrophages (TAMs) are regulators of extracellular matrix (ECM) remodeling and metastatic progression, the main cause of cancer-associated death. We found that disabled 2 mitogen-responsive phosphoprotein (DAB2) is highly expressed in tumor-infiltrating TAMs and its genetic ablation significantly impairs lung metastasis formation. DAB2-expressing TAMs, mainly localized along the tumor invasive front, participate in integrin recycling, ECM remodeling and directional migration in a tridimensional matrix. DAB2+ macrophages escort the invasive dissemination of cancer cells by a mechanosensing pathway requiring the transcription factor Yes-Associated Protein. In human lobular breast and gastric carcinomas, DAB2+ TAMs correlated with a poor clinical outcome, identifying DAB2 as potential prognostic biomarker for cancer patient stratification. DAB2 is therefore central for the pro-metastatic activity of TAMs.
Disabled homolog 2 controls prometastatic activity of tumor-associated macrophages / Marigo, Ilaria; Trovato, Rosalinda; Hofer, Francesca; Ingangi, Vincenzo; DE Sanctis, Francesco; Ugel, Stefano; Cane, Stefania; Simonelli, Anna; Lamolinara, Alessia; Iezzi, Manuela; Fassan, Matteo; Rugge, Massimo; Boschi, Federico; Borile, Giulia; Eisenhaure, Thomas; Sarkizova, Siranush; Lieb, David; Hacohen, Nir; Azzolin, Luca; Piccolo, Stefano; Lawlor, Rita; Scarpa, Aldo; Carbognin, Luisa; Bria, Emilio; Bicciato, Silvio; Murray, Peter J; Bronte, Vincenzo. - In: CANCER DISCOVERY. - ISSN 2159-8274. - 10:11(2020), pp. 1758-1773. [10.1158/2159-8290.CD-20-0036]
Disabled homolog 2 controls prometastatic activity of tumor-associated macrophages
Bicciato, Silvio;
2020
Abstract
Tumor-associated macrophages (TAMs) are regulators of extracellular matrix (ECM) remodeling and metastatic progression, the main cause of cancer-associated death. We found that disabled 2 mitogen-responsive phosphoprotein (DAB2) is highly expressed in tumor-infiltrating TAMs and its genetic ablation significantly impairs lung metastasis formation. DAB2-expressing TAMs, mainly localized along the tumor invasive front, participate in integrin recycling, ECM remodeling and directional migration in a tridimensional matrix. DAB2+ macrophages escort the invasive dissemination of cancer cells by a mechanosensing pathway requiring the transcription factor Yes-Associated Protein. In human lobular breast and gastric carcinomas, DAB2+ TAMs correlated with a poor clinical outcome, identifying DAB2 as potential prognostic biomarker for cancer patient stratification. DAB2 is therefore central for the pro-metastatic activity of TAMs.File | Dimensione | Formato | |
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