Shetzer Yoav, Solomon Hilla, Koifman Gabriela, Molchadsky Alina, Horesh Stav, Rotter Varda
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Carcinogenesis. 2014 Jun;35(6):1196-208. doi: 10.1093/carcin/bgu073. Epub 2014 Mar 21.
It is well accepted that expression of mutant p53 involves the gain of oncogenic-specific activities accentuating the malignant phenotype. Depending on the specific cancer type, mutant p53 can contribute to either the early or the late events of the multiphase process underlying the transformation of a normal cell into a cancerous one. This multifactorial system is evident in ~50% of human cancers. Mutant p53 was shown to interfere with a variety of cellular functions that lead to augmented cell survival, cellular plasticity, aberration of DNA repair machinery and other effects. All these effects culminate in the acquisition of drug resistance often seen in cancer cells. Interestingly, drug resistance has also been suggested to be associated with cancer stem cells (CSCs), which reside within growing tumors. The notion that p53 plays a regulatory role in the life of stem cells, coupled with the observations that p53 mutations may contribute to the evolvement of CSCs makes it challenging to speculate that drug resistance and cancer recurrence are mediated by CSCs expressing mutant p53.
人们普遍认为，突变型p53的表达涉及致癌特异性活性的增强，从而加剧恶性表型。根据具体的癌症类型，突变型p53可促成正常细胞转变为癌细胞这一多阶段过程的早期或晚期事件。这种多因素系统在约50%的人类癌症中很明显。研究表明，突变型p53会干扰多种细胞功能，导致细胞存活率提高、细胞可塑性增强、DNA修复机制异常及其他影响。所有这些影响最终导致癌细胞中常见的耐药性的产生。有趣的是，耐药性也被认为与存在于不断生长的肿瘤中的癌症干细胞（CSCs）有关。p53在干细胞生命中起调节作用这一观点，再加上p53突变可能促成癌症干细胞进化的观察结果，使得推测耐药性和癌症复发是由表达突变型p53的癌症干细胞介导的变得具有挑战性。
