Function of the Developmental Transcription Factor SALL4 in Cancer

Up-regulation of some developmental genes has been observed in cancerous tissues and cancer cells. Sal-like 4 (SALL4), a member of the homologs of Dorosophila spalt (sal) gene, plays a key role in early development and organogenesis. SALL4 encodes a C2H2 multiple zinc finger protein, and is a causative gene for Okihiro/Duane radial ray syndrome, the major symptoms of which are limb malformations and ocular anomalies [1,2]. Genomes of these patients have point mutations in the SALL4 coding sequence, which is thought to cause a loss of SALL4 function. A knockout mouse study has shown that SALL4 null mutant is embryonic lethal, and SALL4 is required for embryonic stem cell proliferation [3]. SALL4 heterozygous mouse exhibits dysplasia of anus, colon, heart, brain and kidney. The authors furthermore have revealed that SALL4 localizes to heterochromatin regions in nuclei of embryonic stem cells. During organ regeneration observed in lower vertebrates, the developmental genes are re-activated. The SALL4 signal has been detected in regenerating Xenopus limb blastema [4]. A blastema tissue is formed at a regenerating part of damaged organ. It contains cells having abilities for growth and differentiation. These studies indicate that SALL4 is a factor for vertebrate development and organogenesis.