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Interplay between HMGA and TP53 in cell cycle control along tumor progression

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Abstract

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.

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Funding

We would like to thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Brazil), Fundação de Amparo à Pesquisa Carlos Chagas Filho (FAPERJ—Brazil), Swiss Bridge Foundation and Associazione Italiana Ricerca sul Cancro (AIRC—Italy) for the financial support for this study.

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  1. Programa de Carcinogênese Molecular, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37-6th floor-Centro, 20231-050, Rio de Janeiro, RJ, Brazil

    Nathalia Meireles Da Costa & Luis Felipe Ribeiro Pinto

  2. Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Prédio de Ciências da Saúde-Cidade Universitária, Ilha do Fundão, A. Carlos Chagas, 373-Bloco F, Sala 26, 21941-902, Rio de Janeiro, RJ, Brazil

    Antonio Palumbo Jr & Luiz Eurico Nasciutti

  3. Istituto di Endocrinologia e Oncologia Sperimentale-CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Naples, Italy

    Marco De Martino & Alfredo Fusco

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  1. Nathalia Meireles Da Costa
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Meireles Da Costa, N., Palumbo, A., De Martino, M. et al. Interplay between HMGA and TP53 in cell cycle control along tumor progression. Cell. Mol. Life Sci. 78, 817–831 (2021). https://doi.org/10.1007/s00018-020-03634-4

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