Loss of Dok-3 in Non-tumor Cells Induces Malignant Transformation of Benign Epithelial Tumor Cells of the Intestine.

ABSTRACT: The fundamental difference between benign and malignant tumors lies in their invasive ability. It is believed that malignant conversion of benign tumor cells is induced by a tumor cell-intrinsic accumulation of driver gene mutations. Here, we found that disruption of the Dok-3 tumor suppressor gene led to malignant progression in the intestinal benign tumor model ApcMin/+ mice. However, Dok-3 gene expression was undetectable in epithelial tumor cells and the transplantation of bone marrow cells lacking the Dok-3 gene-induced malignant conversion of epithelial tumor cells in ApcMin/+ mice, indicating a previously unrecognized tumor cell-extrinsic mechanism. Moreover, the Dok-3 loss-induced tumor invasion in ApcMin/+ mice required CD4⁺ and CD8⁺ T ly

SUBMITTER: Arimura S 

PROVIDER: S-EPMC10035524 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature