The high mobility group A1 molecular switch: turning on cancer - can we turn it off?

Introduction: Emerging evidence demonstrates that the high mobility group A1 (HMGA1) chromatin remodeling protein is a key molecular switch required by cancer cells for tumor progression and a poorly differentiated, stem-like state. Because the HMGA1 gene and proteins are expressed at high levels in all aggressive tumors studied to date, research is needed to determine how to 'turn off' this master regulatory switch in cancer.

Areas Covered: In this review, we describe prior studies that underscore the central role of HMGA1 in refractory cancers and we discuss approaches to target HMGA1 in cancer therapy.

HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression genes during lymphoid tumorigenesis.

Background: Although the high mobility group A1 (HMGA1) gene is widely overexpressed in diverse cancers and portends a poor prognosis in some tumors, the molecular mechanisms that mediate its role in transformation have remained elusive. HMGA1 functions as a potent oncogene in cultured cells and induces aggressive lymphoid tumors in transgenic mice. Because HMGA1 chromatin remodeling proteins regulate transcription, HMGA1 is thought to drive malignant transformation by modulating expression of specific genes.