SALL4: An emerging cancer biomarker and target

SALL4 is a transcription factor that plays essential roles in maintaining self-renewal and pluripotency of embryonic stem cells (ESCs). In fully differentiated cells, SALL4 expression is down-regulated or silenced. Accumulating evidence suggest that SALL4 expression is reactivated in cancer. Constitutive expression of SALL4 transgene readily induces acute myeloid leukemia (AML) development in mice. Gain- and loss-of-function studies reveal that SALL4 regulates proliferation, apoptosis, invasive migration, chemoresistance, and the maintenance of cancer stem cells (CSCs). SALL4 controls the expression of its downstream genes through both genetic and epigenetic mechanisms. High level of SALL4 expression is detected in cancer patients, which predicts adverse progression and poor outcome. Moreover, targeted inhibition of SALL4 has shown efficient therapeutic effects on cancer. We have summarized the recent advances in the biology of SALL4 with a focus on its role in cancer. Further study of the oncogenic functions of SALL4 and the underlying molecular mechanisms will shed light on cancer biology and provide new implications for cancer diagnostics and therapy.