The high mobility group A (
HMGA) proteins are found to be aberrantly expressed in several
tumors. Studies (in vitro and in vivo) have shown that
HMGA protein overexpression has a causative role in
carcinogenesis process.
HMGA proteins regulate cell cycle progression through distinct mechanisms which strongly influence its normal dynamics along malignant transformation.
Tumor protein p53 (TP53) is the most frequently altered gene in
cancer. The loss of its activity is recognized as the fall of a barrier that enables neoplastic transformation. Among the different functions, TP53 signaling pathway is tightly involved in control of cell cycle, with cell cycle arrest being the main biological outcome observed upon p53 activation, which prevents accumulation of damaged
DNA, as well as
genomic instability. Therefore, the interaction and opposing effects of
HMGA and p53
proteins on regulation of cell cycle in normal and
tumor cells are discussed in this review.
HMGA proteins and p53 may reciprocally regulate the expression and/or activity of each other, leading to the counteraction of their regulation mechanisms at different stages of the cell cycle. The existence of a functional crosstalk between these
proteins in the control of cell cycle could open the possibility of targeting
HMGA and p53 in combination with other therapeutic strategies, particularly those that target cell cycle regulation, to improve the management and prognosis of
cancer patients.