Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro"-Policlinico, Piazza G. Cesare, 11, 70124 Bari, Italy.
Institute of Biomembranes, Bioenergetics and Molecular Biotechnology, National Research Council-CNR, Via Amendola 122/O, 70126 Bari, Italy.
Int J Mol Sci. 2019 Apr 10;20(7):1776. doi: 10.3390/ijms20071776.
Chemosensitivity is a crucial feature for all tumours so that they can be successfully treated, but the huge heterogeneity of these diseases, to be intended both inter- and intra-tumour, makes it a hard-to-win battle. Indeed, this genotypic and phenotypic variety, together with the adaptability of tumours, results in a plethora of chemoresistance acquisition mechanisms strongly affecting the effectiveness of treatments at different levels. Tripartite motif (TRIM) proteins are shown to be involved in some of these mechanisms thanks to their E3-ubiquitin ligase activity, but also to other activities they can exert in several cellular pathways. Undoubtedly, the ability to regulate the stability and activity of the p53 tumour suppressor protein, shared by many of the TRIMs, represents the preeminent link between this protein family and chemoresistance. Indeed, they can modulate p53 degradation, localization and subset of transactivated target genes, shifting the cellular response towards a cytoprotective or cytotoxic reaction to whatever damage induced by therapy, sometimes in a cellular-dependent way. The involvement in other chemoresistance acquisition mechanisms, independent by p53, is known, affecting pivotal processes like PI3K/Akt/NF-κB signalling transduction or Wnt/beta catenin pathway, to name a few. Hence, the inhibition or the enhancement of TRIM proteins functionality could be worth investigating to better understand chemoresistance and as a strategy to increase effectiveness of anticancer therapies.
化疗敏感性是所有肿瘤的关键特征，使其能够得到成功治疗，但这些疾病的巨大异质性，无论是在肿瘤之间还是肿瘤内部，都使得这成为一场艰难的战斗。事实上，这种基因型和表型的多样性，加上肿瘤的适应性，导致了大量的化疗耐药获得机制，强烈影响着不同层面治疗的效果。三基序（TRIM）蛋白由于其 E3-泛素连接酶活性，以及它们在几种细胞途径中发挥的其他活性，被证明参与了其中的一些机制。毫无疑问，许多 TRIM 蛋白共同具有的调节 p53 肿瘤抑制蛋白稳定性和活性的能力，代表了该蛋白家族与化疗耐药性之间的首要联系。事实上，它们可以调节 p53 的降解、定位和部分转录激活靶基因，使细胞对治疗诱导的任何损伤产生细胞保护或细胞毒性反应，有时以细胞依赖性的方式。TRIM 蛋白的功能抑制或增强可能值得研究，以更好地理解化疗耐药性，并作为提高抗癌治疗效果的一种策略。
