Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients

Fendler，Annika1,2,3,4; Bauer，Daniel1; Busch，Jonas2,3; Jung，Klaus3,4; Wulf-Goldenberg，Annika5; Kunz，Severine6; Song，Kun7; Myszczyszyn，Adam1; Elezkurtaj，Sefer8; Erguen，Bettina3; Jung，Simone1; Chen，Wei2,7,9; Birchmeier，Walter1,2

2020-12-01

10.1038/s41467-020-14700-7

Nature Communications   影响因子和分区

2041-1723

2041-1723

Current treatments for clear cell renal cell cancer (ccRCC) are insufficient because two-thirds of patients with metastases progress within two years. Here we report the identification and characterization of a cancer stem cell (CSC) population in ccRCC. CSCs are quantitatively correlated with tumor aggressiveness and metastasis. Transcriptional profiling and single cell sequencing reveal that these CSCs exhibit an activation of WNT and NOTCH signaling. A significant obstacle to the development of rational treatments has been the discrepancy between model systems and the in vivo situation of patients. To address this, we use CSCs to establish non-adherent sphere cultures, 3D tumor organoids, and xenografts. Treatment with WNT and NOTCH inhibitors blocks the proliferation and self-renewal of CSCs in sphere cultures and organoids, and impairs tumor growth in patient-derived xenografts in mice. These findings suggest that our approach is a promising route towards the development of personalized treatments for individual patients.

SCI

英语

NI期刊

其他

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000564266200009

NATURE PUBLISHING GROUP

2-s2.0-85079640862

Scopus

1.Cancer Research Program,Max Delbrueck Center for Molecular Medicine (MDC) in the Helmholtz Association,Berlin,Germany
2.Berlin Institute of Health (BIH),Berlin,Germany
3.Department of Urology,Charité-University Medicine,Berlin,Germany
4.Berlin Institute for Urologic Research,Berlin,Germany
5.Experimental Pharmacology and Oncology GmbH (EPO),Berlin,Germany
6.Electron Microscopy Core Facility,Max Delbrueck Center for Molecular Medicine (MDC) in the Helmholtz Association,Berlin,Germany
7.Berlin Institute for Medical Systems Biology (BIMSB),Max Delbrueck Center for Molecular Medicine (MDC) in the Helmholtz Association,Berlin,Germany
8.Department of Pathology,Charité-University Medicine,Berlin,Germany
9.Department of Biology,Southern University of Science and Technology,Shenzhen,China

Fendler，Annika,Bauer，Daniel,Busch，Jonas,et al. Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients[J]. Nature Communications,2020,11(1).

Fendler，Annika.,Bauer，Daniel.,Busch，Jonas.,Jung，Klaus.,Wulf-Goldenberg，Annika.,...&Birchmeier，Walter.(2020).Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients.Nature Communications,11(1).

Fendler，Annika,et al."Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients".Nature Communications 11.1(2020).