The high mobility group A1 gene: transforming inflammatory signals into cancer?

Abstract

High mobility group A1 (HMGA1) is highly expressed during embryogenesis and in poorly differentiated cancers, and high levels portend a poor prognosis in some tumors. HMGA1 induces oncogenic transformation in cultured cells and causes aggressive cancers in transgenic mice, whereas blocking it interferes with transformation in experimental models. These findings suggest a pivotal role for HMGA1 in cancer. This review focuses on two recently described HMGA1 transcriptional targets that mediate inflammatory signals and drive malignant transformation because they could serve as biomarkers or therapeutic targets. Further elucidation of HMGA1 function in transformation promises to have a major impact on our war on cancer.

Figure 1

Induction of HMGA1 results in binding to the minor groove at AT-rich regions in chromatin and recruitment of transcriptional regulators. NF-κB (p65/p50) and other transcription factors (TF-x, TF-y) are shown, which leads to the formation of the enhanceosome and activation of oncogenic pathways.