Loss of myeloid-specific lamin A/C drives lung metastasis through Gfi-1 and C/EBPε-mediated granulocytic differentiation.

ABSTRACT: The immune-suppressive tumor microenvironment promotes metastatic spread and outgrowth. One of the major contributors is tumor-associated myeloid cells. However, the molecular mechanisms regulating their differentiation and function are not well understood. Here we report lamin A/C, a nuclear lamina protein associated with chromatin remodeling, was one of the critical regulators in cellular reprogramming of tumor-associated myeloid cells. Using myeloid-specific lamin A/C knockout mice and triple-negative breast cancer (TNBC) mouse models, we discovered that the loss of lamin A/C drives CD11b⁺ Ly6G⁺ granulocytic lineage differentiation, alters the production of inflammatory chemokines, decreases host antitumor immunity, and increases metastasis. The underlying mechanis

SUBMITTER: Ishii H 

PROVIDER: S-EPMC7282947 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature