| First Author | Marigo I | Year | 2020 |
| Journal | Cancer Discov | Volume | 10 |
| Issue | 11 | Pages | 1758-1773 |
| PubMed ID | 32651166 | Mgi Jnum | J:299293 |
| Mgi Id | MGI:6478476 | Doi | 10.1158/2159-8290.CD-20-0036 |
| Citation | Marigo I, et al. (2020) Disabled Homolog 2 Controls Prometastatic Activity of Tumor-Associated Macrophages. Cancer Discov 10(11):1758-1773 |
| abstractText | Tumor-associated macrophages (TAM) are regulators of extracellular matrix (ECM) remodeling and metastatic progression, the main cause of cancer-associated death. We found that disabled homolog 2 mitogen-responsive phosphoprotein (DAB2) is highly expressed in tumor-infiltrating TAMs and that 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 YAP. In human lobular breast and gastric carcinomas, DAB2(+) TAMs correlated with a poor clinical outcome, identifying DAB2 as potential prognostic biomarker for stratification of patients with cancer. DAB2 is therefore central for the prometastatic activity of TAMs. SIGNIFICANCE: DAB2 expression in macrophages is essential for metastasis formation but not primary tumor growth. Mechanosensing cues, activating the complex YAP-TAZ, regulate DAB2 in macrophages, which in turn controls integrin recycling and ECM remodeling in 3-D tissue matrix. The presence of DAB2(+) TAMs in patients with cancer correlates with worse prognosis.This article is highlighted in the In This Issue feature, p. 1611. |
