Cordani Marco, Pacchiana Raffaella, Butera Giovanna, D'Orazi Gabriella, Scarpa Aldo, Donadelli Massimo
Department of Neuroscience, Biomedicine and Movement, Biochemistry Section, University of Verona, Verona, Italy.
Unit of Cellular Networks and Therapeutic Targets, Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute - IRCCS, Rome, Italy.
Cancer Lett. 2016 Jul 1;376(2):303-9. doi: 10.1016/j.canlet.2016.03.046. Epub 2016 Apr 1.
An ever-increasing number of studies highlight the role of mutant p53 proteins in the alteration of cancer cell secretome and in the modification of tumour microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge of the molecular mechanisms underlying the interplay between mutant p53 proteins and the microenvironment is becoming fundamental for the identification of both efficient anticancer therapeutic strategies and novel serum biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight data from available literature, suggesting that mutant p53 proteins are able to (i) alter the secretion of enzymes involved in the modulation of extracellular matrix components; (ii) alter the secretion of inflammatory cytokines; (iii) increase the extracellular acidification; and (iv) regulate the crosstalk between cancer and stromal cells.
越来越多的研究强调了突变型p53蛋白在癌细胞分泌组改变以及肿瘤微环境修饰中的作用，维持着癌细胞的侵袭表型。了解突变型p53蛋白与微环境之间相互作用的分子机制，对于确定有效的抗癌治疗策略和新型血清生物标志物都至关重要。在本综述中，我们总结了有关携带突变型TP53基因的癌细胞对分泌分子调控的新发现。特别是，我们突出了现有文献中的数据，表明突变型p53蛋白能够：（i）改变参与细胞外基质成分调节的酶的分泌；（ii）改变炎性细胞因子的分泌；（iii）增加细胞外酸化；以及（iv）调节癌细胞与基质细胞之间的相互作用。
