Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells

• DOI: 10.1172/jci.insight.125138
• Publication Date: 2019-02-20T16:01:38Z
• Authors: Hideyuki Shimizu; Shoichiro Takeishi; Hirokazu Nakatsumi; Keiichi I. Nakayama
• Keywords: 0303 health sciences; F-Box-WD Repeat-Containing Protein 7; Datasets as Topic; Bone Marrow Cells; Breast Neoplasms; Kaplan-Meier Estimate; Antineoplastic Agents, Phytogenic; 3. Good health; Cohort Studies; Gene Expression Regulation, Neoplastic; Disease Models, Animal; Gene Knockout Techniques; Mice; 03 medical and health sciences; Bone Marrow; Drug Resistance, Neoplasm; Cell Line, Tumor; MCF-7 Cells; Animals; Humans; Female; Breast; Cell Proliferation

Dormant cancer cells known as disseminated tumor (DTCs) are often present in bone marrow of breast patients. These DTCs thought to be responsible for the incurable recurrence cancer. The mechanism underlying long-term maintenance remains unclear, however. Here, we show that Fbxw7 is essential dormancy. Genetic ablation disrupted quiescence DTCs, rendering them proliferative, mouse xenograft and allograft models. Fbxw7-deficient were significantly depleted by treatment with paclitaxel, suggesting cell proliferation induced sensitized chemotherapy. combination chemotherapy reduced number even when applied after dissemination. Mice injected survived longer resection subsequent than did those wild-type cells. Furthermore, database analysis revealed patients whose tumors expressed FBXW7 at a high level had poorer prognosis low expression level. Our results suggest wake-up strategy based on inhibition might value conventional