Supplemental Figure 5 from EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1

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posted on 2023-03-30, 23:11 authored by Yung-Sheng Chang, Wei-Yu Chen, Juan Juan Yin, Heather Sheppard-Tillman, Jiaoti Huang, Yen-Nien Liu

(A and B) TWIST1 (A) and miR-1 (B) expressions in patient samples at different clinical stages in the prostate cancer samples collected and analyzed at MSKCC. * vs. T2A. * p<0.05, ** p<0.01. (C and D) Kaplan-Meier curve showing the survival rate relative to TWIST1 (C) and miR-1 (D) expressions in prostate cancer samples collected and analyzed at MSKCC. Patient groups with high TWIST1 and low miR-1 levels (blue line) had a lower survival rate compared to groups with low TWIST1 and high miR-1 levels (black line). Hazard ratios (log rank) were 1.664 (TWIST1) and 1.907 (miR-1). X-axes show the time in months, and Y-axes show percentage survival (log rank (Mantel-Cox) test p=0.0026 (TWIST1) and p=0.0017 (miR-1)). (E) H&E and IHC staining of bone metastases with an antibody specific for TWIST1 in mouse from tumor-bearing mice inoculated with parental RasB1 (control), RasB1/miR-1 (miR-1/EV), and EGFR-rescued RasB1/miR-1 (miR-1/EGFR) cells. B: bone; T: tumor; BM: bone marrow. Scale bars represent 50 µm.

History

ARTICLE ABSTRACT

Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis. Cancer Res; 75(15); 3077–86. ©2015 AACR.