| First Author | Bui T | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 3 | Pages | 589-602.e6 |
| PubMed ID | 31618629 | Mgi Jnum | J:286803 |
| Mgi Id | MGI:6390748 | Doi | 10.1016/j.celrep.2019.09.004 |
| Citation | Bui T, et al. (2019) Functional Redundancy between beta1 and beta3 Integrin in Activating the IR/Akt/mTORC1 Signaling Axis to Promote ErbB2-Driven Breast Cancer. Cell Rep 29(3):589-602.e6 |
| abstractText | Integrin receptors coordinate cell adhesion to the extracellular matrix (ECM) to facilitate many cellular processes during malignant transformation. Despite their pro-tumorigenic roles, therapies targeting integrins remain limited. Here, we provide genetic evidence supporting a functional redundancy between beta1 and beta3 integrin during breast cancer progression. Although ablation of beta1 or beta3 integrin alone has limited effects on ErbB2-driven mammary tumorigenesis, deletion of both receptors resulted in a significant delay in tumor onset with a corresponding impairment in lung metastasis. Mechanistically, stiff ECM cooperates with integrin receptors to recruit insulin receptors (IRs) to focal adhesion through the formation of integrin/IR complexes, thereby preventing their lysosomal degradation. beta1/beta3 integrin-deficient tumors that eventually emerged exhibit impaired Akt/mTORC1 activity. Murine and human breast cancers exhibiting enhanced integrin-dependent activity also display elevated IR/Akt/mTORC1 signaling activity. Together, these observations argue that integrin/IR crosstalk transduces mechanical cues from the tumor microenvironment to promote ErbB2-dependent breast cancer progression. |
