Study in mice and human cells describes reactivation of an important tumour suppressive gene using a vegetable extract thus offering a promising strategy for 癌症 治疗
癌症预防 是全球第二大死亡原因。 在癌症中，多种遗传和表观遗传改变要么是遗传的，要么是体细胞获得的。 这些与癌症发展相关的改变有两种不同的类型——(a) 细胞癌基因的激活或“功能获得”和 (b) 肿瘤抑制基因的失活或“功能丧失”。 瘤 抑制基因通常抑制细胞增殖和肿瘤发展。 如果它们失活，细胞增殖的负调节因子就会丢失，这会导致肿瘤细胞的异常增殖。 肿瘤抑制因子的再激活作为治疗人类的潜在策略 癌症 已经进行了研究，但没有像致癌蛋白的抑制研究那样详细地探索。
A potent tumour suppressive gene called PTEN is the most commonly mutated, deleted, down-regulated or silenced gene in human cancers. PTEN is a phosphatase which is active as a dimer at the plasma membrane. If PTEN mutations are inherited then it can cause syndromes like susceptibility to 癌症 and developmental defects. Tumour cells exhibit low levels of PTEN. Restoration of normal levels of PTEN in cancer cells can allow PTEN gene to continue its tumour suppressive activity. It is known that PTEN dimer formation and its recruitment at the membrane is critical for its function, however, the exact molecular mechanisms of this are still unknown.
在发表的一项研究 科学 17 年 2019 月 1 日，描述了一种涉及 PTEN 的新途径，它作为肿瘤生长控制的调节剂，对癌症的发展很重要。 研究人员研究了一种名为 WWP3 的基因，该基因已知在癌症的发展中起重要作用，并产生一种泛素 E1 连接酶。 这种酶是一种 PTEN 相互作用蛋白，它通过抑制 PTEN 的二聚化、膜募集及其功能来抑制 PTEN 的肿瘤抑制活性。 WWP3 在许多癌症中得到基因增强，包括乳腺癌、前列腺癌和肝癌。 在探索了这种酶的 3 维结构后，研究人员将一种叫做 indole-3-carbinol (I3C) 的小分子列入候选名单，它可以抑制这种酶的活性。 IXNUMXC 是一种天然化合物，是西兰花和其他十字花科植物的成分 蔬菜 其中包括花椰菜、卷心菜、羽衣甘蓝和抱子甘蓝。 众所周知，此类蔬菜是人们饮食中健康的补充，而且以前食用这些蔬菜与降低患癌症的风险有关。
The compound I3C was administered to cancer prone mice (mouse model of prostate 癌症) and into human cell lines and it was seen that I3C inhibited activity of WWP1 by depleting it. This led to restored tumour suppressive power of PTEN. I3C is thus a natural pharmacological inhibitor of WWP1 which can trigger PTEN reactivation. WWP1 appeared to be a direct MYC target gene (protooncogene) for MYC driven tumorigenesis or formation of tumours. The study showed that perturbation of WWP1 is enough to restore PTEN’s tumour suppression activity.
It may not be feasible to achieve these anti-cancer benefits from simply consuming broccoli and other cruciferous vegetables as food since very high levels of daily consumption would be needed. Further investigations need to focus on studying functions of WWP1 and developing its inhibitors as the current study establishes that inhibition of WWP1-PTEN pathway is promising when there is presence of tumour-driven MYC overexpression or abnormal PTEN function. The current study paves a way for a new 癌症 treatment using tumour suppressor reactivation approach.
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来源（S）
李 Y. 等。 2019. 通过抑制 MYC-WWP1 抑制途径重新激活 PTEN 肿瘤抑制因子用于癌症治疗。 科学，364 (6441)。 https://doi.org/10.1126/science.aau0159
