Figure 7.

Elf3 could serve as a potential therapeutic target in CRC. (a,b) Knockdown of Elf3 inhibited growth of xenograft in nude mice. Human CRC HCT116 cells were injected subcutaneously into the right armpit to establish a xenograft model, and specific siRNA for Elf3 or control siRNA was introduced to tumors cells by in vivo-jetPEI nanoparticles. The sizes of in situ and resected tumors treated with/without Elf3 siRNAs in the last time point (12 days after first injection) are shown in panels (a) and (b), respectively. (c) Tumor growth curves in the Elf3 siRNA group and the control group (P<0.001, t-test for tumor sizes at the last time point). Knockdown of Elf3 significantly suppressed xenograft tumor progression. (d–f) Immunofluorescence showing knockdown of Elf3 dramatically decreased the level of β-catenin in xenograft CRC tumors. Representative immunofluorescence images are shown in (d), Statistical results are indicated in (e) and (f). (g) Proposed model for Elf3-mediated β-catenin signaling. The amplification of ELF3 gene in colorectal epithelial cells leads to upregulation of Elf3 mRNA, causing transactivation of β-catenin. In synergy with the well-established Wnt-dependent regulation at protein level, Elf3 induces substantial accumulation of β-catenin in CRC cells, leading to upregulation of pro-oncogenic effector genes (c-myc, CCND1, MMP-7, etc) and increased malignant phenotypes