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 pro-metastatic activity of tumor-associated macrophages

Rosalinda Trovato;Francesca Hofer;Francesco De Sanctis;Stefano Ugel;Stefania Canè;Anna Simonelli;Federico Boschi;Rita Lawlor;Aldo Scarpa;Vincenzo Bronte
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.
Tumor-associated macrophages (TAMs), extracellular matrix (ECM), metastatic progression, 2 mitogen-responsive phosphoprotein (DAB2)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1021540
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