60529

ALX4

Homeoproteins, a family of transcription factors that have conserved homeobox domains, play critical roles in embryonic development in a wide range of species. Accumulating studies have revealed that homeoproteins are aberrantly expressed in multiple tumors and function as either tumor promoters or suppressors. In this study, we show that two homeoproteins, HOXB13 and ALX4, are associated with epithelial to mesenchymal transition (EMT) and invasion of ovarian cancer cells. HOXB13 and ALX4 formed a complex in cells, and exogenous expression of either protein promoted EMT and invasion. Conversely, depletion of either protein suppressed invasion and induced reversion of EMT. SLUG is a C2H2-type zinc-finger transcription factor that promotes EMT in various cell lines. Knockdown of HOXB13 or ALX4 suppressed SLUG expression, and exogenous expression of either protein promoted SLUG expression. Finally, we showed that SLUG expression was essential for the HOXB13- or ALX4-mediated EMT and invasion. Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of ovarian cancer cells.

Aristaless-like homeobox-4 (ALX4), a member of the Aristaless-like homeobox family, has been found to be involved in tumor cell proliferation, migration, and invasion. However, the role of ALX4 in hepatocellular carcinoma (HCC) remains largely unclear. Therefore, in this study we investigated the effects of ALX4 on HCC. The study results indicated that the expression of ALX4 was downregulated in HCC tissues and cell lines. Furthermore, we demonstrated that overexpression of ALX4 inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) in HCC cells. We also found that ALX4 had an inhibitory effect on the sonic hedgehog (Shh) signaling pathway. Taken together, the results suggest that ALX4 may be a promising target for HCC treatment.