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.

高流动性A组（HMGA）蛋白被发现在几种肿瘤中异常表达。研究（体外和体内）表明，HMGA蛋白的过度表达在致癌过程中具有致病作用。HMGA蛋白通过不同的机制调节细胞周期进程，这些机制会强烈影响其沿恶性转化的正常动力学。肿瘤蛋白p53（TP53）是癌症中最常改变的基因。其活性的丧失被认为是使肿瘤转化的障碍的下降。在不同的功能中，TP53信号通路紧密参与细胞周期的控制，细胞周期停滞是p53激活后观察到的主要生物学结果，可防止受损DNA的积累以及基因组不稳定。因此，本文综述了HMGA和p53蛋白在正常细胞和肿瘤细胞中对细胞周期调控的相互作用和相反作用。HMGA蛋白和p53可能相互调节彼此的表达和/或活性，从而导致它们在细胞周期不同阶段的调节机制相互抵消。这些蛋白之间在细胞周期控制中存在功能性串扰，可能与其他治疗策略（尤其是针对细胞周期调控的策略）相结合，从而有可能靶向HMGA和p53。