| First Author | Bui T | Year | 2022 |
| Journal | Oncogene | Volume | 41 |
| Issue | 4 | Pages | 527-537 |
| PubMed ID | 34782719 | Mgi Jnum | J:319457 |
| Mgi Id | MGI:6864249 | Doi | 10.1038/s41388-021-02107-7 |
| Citation | Bui T, et al. (2022) Emergence of beta1 integrin-deficient breast tumours from dormancy involves both inactivation of p53 and generation of a permissive tumour microenvironment. Oncogene 41(4):527-537 |
| abstractText | The molecular and cellular mechanisms underlying mammary tumour dormancy and cancer recurrence are unclear and remain to be elucidated. Here, we report that mammary epithelial-specific disruption of beta1 integrin in a murine model of Luminal B human breast cancer drastically impairs tumour growth with proliferation block, apoptosis induction and cellular senescence. beta1 integrin-deficient dormant lesions show activation of the tumour suppressor p53, and tumours that circumvent dormancy possess p53 mutation analogous to those in human disease. We further demonstrate that mammary epithelial deletion of p53 in beta1 integrin-deficient mice fully rescues tumour dormancy and bypasses cellular senescence. Additionally, recurrent beta1 integrin-deficient tumours exhibit fibrosis with increased cancer-associated fibroblast infiltration and extracellular matrix deposition, absent in fast-growing beta1 integrin/p53-deficient lesions. Taken together, these observations argue that beta1 integrin modulates p53-dependent cellular senescence resulting in tumour dormancy and that pro-tumourigenic stromal cues and intrinsic genetic mutation are required for dormancy exit. |
