Fig. 6: WNT4/TCF7L1 upregulate cell migration and the NED of PCa cells.
From: TCF7L1 regulates cytokine response and neuroendocrine differentiation of prostate cancer
A–D Cell migration (A, B) and invasion (C, D) assay of LNCaP and C4-2 cells with stable overexpression of TCF7L1 or an empty vector (EV) following 100 ng/ml WNT4 treatment for 24 h. * vs. the EV + PBS. Data are presented as the mean ± SEM, n = 3. *p < 0.05, **p < 0.01, ***p < 0.001; by a two-way ANOVA. E–H Cell migration (E, F) and invasion (G, H) assays of PC3 cells with overexpression of a nontarget control (NC) or TCF7L1 shRNA vector following 100 ng/ml WNT4 treatment for 24 h. * vs. PBS; # vs. the NC. Data are presented as the mean ± SEM, n = 3. *p < 0.05, **p < 0.01, ***p < 0.001; by a two-way ANOVA. I, J IHC staining and analysis of subcutaneous tumors with antibodies specific for TCF7L1, IL-8, CXCR2, ENO2, and PCNA in mice harboring PC3 cells expressing the NC or TCF7L1 shRNA vectors. Scale bars represent 100 µm. K Proposed model for androgen deprivation-induced WNT4/TCF7L1 signaling crosstalk with IL-8/CXCR2 signaling. ADT induced activation of the WNT4/TCF7L1 pathway, leading to upregulation of IL-8 and CXCR2. Overexpression of IL-8 and CXCR2 drives ADT resistance and NED of PCa.
