American Association for Cancer Research
Browse
00085472can192733-sup-228309_2_supp_6223157_q8snrt.docx (52.69 kB)

Supplementary Data from Spatiotemporal Regulation of ΔNp63 by TGFβ-Regulated miRNAs Is Essential for Cancer Metastasis

Download (52.69 kB)
journal contribution
posted on 2023-03-31, 03:07 authored by Ngoc H.B. Bui, Marco Napoli, Andrew John Davis, Hussein A. Abbas, Kimal Rajapakshe, Cristian Coarfa, Elsa R. Flores

Supplementary information includes Supplementary figure legends, Materials and Methods, and Reference

Funding

NCI Outstanding Investigator

Moffitt Distinguished Scholar

Scholar of the Leukemia and Lymphoma Society

Rita Allen Foundation

the V Foundation for Cancer Research

Flow Cytometry Core

National Institute of Allergy and Infectious Diseases

Find out more...

Biostatistics and Bioinformatics Core

Moffitt Cancer Center

NCI-designated Comprehensive Cancer Center

History

ARTICLE ABSTRACT

ΔNp63 is a transcription factor of the p53 family and has crucial functions in normal development and disease. The expression pattern of ΔNp63 in human cancer suggests dynamic regulation of this isoform during cancer progression and metastasis. Many primary and metastatic tumors express high levels of ΔNp63, while ΔNp63 loss is crucial for tumor dissemination, indicating an oscillatory expression of ΔNp63 during cancer progression. Here, we use genetically engineered orthotopic mouse models of breast cancer to show that while depletion of ΔNp63 inhibits primary mammary adenocarcinoma development, oscillatory expression of ΔNp63 in established tumors is crucial for metastatic dissemination in breast cancer. A TGFβ-regulated miRNA network acted as upstream regulators of this oscillatory expression of ΔNp63 during cancer progression. This work sheds light on the pleiotropic roles of ΔNp63 in cancer and unveils critical functions of TGFβ in the metastatic process. This study unveils TGFβ signaling and a network of four miRNAs as upstream regulators of ΔNp63, providing key information for the development of therapeutic strategies to treat cancers that commonly overexpress ΔNp63.