Ruan Lingling, Shen Yanting, Lu Ziwen, Shang Dongsheng, Zhao Zhicong, Lu Yongjin, Wu Yanfang, Zhang Yafei, Tu Zhigang, Liu Hanqing
School of Pharmacy, Jiangsu University, Zhenjiang, China.
Institute of Life Sciences, Jiangsu University, Zhenjiang, China.
Clin Exp Pharmacol Physiol. 2017 Sep;44(9):909-913. doi: 10.1111/1440-1681.12794.
A pivotal regulator of cell polarity and homeostasis, partitioning-defective protein 6 (Par6) forms multicomponent complexes that not only regulate cell polarity and stabilize cell morphology, but have also been demonstrated to participate in the proliferation, migration and invasion of cancer cells. The transforming growth factor (TGF)-β and extracellular signal-regulated kinase (Erk) 1/2 pathways are the most thoroughly studied pathways involving Par6 in many cancers. Aurothiomalate has been used to disrupt the interaction between Par6 and atypical protein kinase C within the multicomponent complexes, and has been shown to effectively block transformed growth and metastasis in vitro and/or in vivo in a variety of cancers, including pancreatic, prostate and lung cancers, as well as alveolar rhabdomyosarcoma. It is likely that with further revelations regarding the critical roles of Par6 in cancer initiation, progression and metastasis, targeted therapies against Par6 will be discovered and prove effective preclinically, and hopefully clinically, in cancer treatment.
作为细胞极性和内环境稳定的关键调节因子，Par6（分隔缺陷蛋白6）形成多组分复合物，不仅调节细胞极性并稳定细胞形态，还被证明参与癌细胞的增殖、迁移和侵袭。转化生长因子（TGF）-β和细胞外信号调节激酶（Erk）1/2信号通路是在许多癌症中涉及Par6的研究最为深入的信号通路。金硫苹果酸盐已被用于破坏多组分复合物中Par6与非典型蛋白激酶C之间的相互作用，并已显示在体外和/或体内能有效阻断多种癌症（包括胰腺癌、前列腺癌和肺癌以及肺泡横纹肌肉瘤）的转化生长和转移。随着对Par6在癌症发生、发展和转移中的关键作用有更多的揭示，有望发现针对Par6的靶向治疗方法，并在临床前以及有望在临床上证明其在癌症治疗中的有效性。
