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Figure S3. Pathways regulated by ∆Np63-induced and -repressed genes.

Figure S5. TGFβ regulates ΀�Np63 expression via miR-22-3p, miR-30a-5p, miR-203a-3p and miR-222-3p.

Figure S6. Correlation between �Np63 and microRNAs expression in cancer cell lines.

Figure S1. �Np63 promotes breast cancer cell growth in vivo

Table S4. PCA scores for each patient in the four COCA molecular subtypes from TCGA.

Table S2. Differential expressed microRNAs in MCF10DCIS cells treated with TGFβ.

Figure S2. �Np63 expression is essential for breast cancer lung colonization.

Table S1. List of pathways enriched in ∆Np63-induced and -repressed gene signatures.

Figure S4. TGFβ inhibits expression of ΀�Np63 via canonical Smad-dependent signaling in breast cancer.

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.Significance: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.

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

Table S3. List of 64 TGFβ-induced microRNAs that are predicted to have binding sites to 3'UTR of p63 by miRWalk algorithm.