p53突变在三阴性乳腺癌转移中的作用及机制

The role and mechanisms of mutant-p53 in metastasis of triple-negative breast cancers

三阴性[雌激素(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)与人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER-2)均为阴性]乳腺癌(triple negative breast cancer,TNBC)是一个具有特殊生物学行为及临床特征的乳腺癌亚型,而转移是其发病和致死的最主要原因。最近的研究表明,在TNBC中,高频率的p53突变能使p63转录活性丧失,此外,Shar p1作为p53突变/p63调节的主要基因之一,它抑制乳腺癌转移的功能亦丧失,而Shar p1之所以能抑制TNBC的浸润性转移,是因为Sharp1是促进缺氧诱导因子(hypoxia-inducible factor,HIF)降解以及减弱HIF诱导癌细胞恶变的重要因子,从而促进TNBC的转移。所以本文通过在中国知网、Pubmed和Highw ire上检索并研究近100篇文献的基础上,就p53突变通过p63/Shar p1/HIF信号通路促进TNBC转移的作用及机制做一综述。

Triple-negative [estrogen receptor（ER）, progesterone receptor（PR） and human epidermal growth factor receptor 2（HER-2） are all negative] breast cancers, a subgroup of breast cancer, have distinct biological and clinical characteristics, of which metastasis is the most significant cause of morbidity and mortality. Recent work revealed that the p63 transcriptional activity could be limited by high mutant-p53 of triple-negative breast cancers. Besides, Sharp1 is the signature of p63-regulated genes, its function of inhibiting metastasis in specific tumors could also be limited. Moreover, metastasis of aggressive triple-negative breast cancers could be suppressed by Sharp1, because Sharp1 can promote degradation of hypoxia-inducible factor（HIF） and blunt HIF-induced malignant cell behavior, which make the tumor metastasis. On the base of retrievaling and studying about one hundred literatures by CNKI, Pubmed and Highwire, this review highlights the role and mechanisms of mutant-p53 in metastasis of triple-negative breast cancers.