Background & Objectives: Chromatin structure is the single most
important feature that distinguishes a cancer cell from a normal cell
histologically. Chromatin remodeling proteins regulate chromatin structure and
high mobility group A (HMGA1) proteins are among the most abundant,
nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b
isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high
levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and
postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells,
while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to
aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is
also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as
ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce
oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1
“transcriptome” is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only
beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we
summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss
studies linking HMGA1 to Alzheimer’s disease and type-2 diabetes.
Conclusion: Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and
possibly for other diseases associated with aberrant HMGA1 expression.
Keywords: High mobility group A1, HMGA, chromatin, cancer, tumor progression, metastasis, genes, cancer stem
cells, embryonic stem cells.
Rights & PermissionsPrintExport