The class I phosphoinositide 3-kinase (PI3K) catalytic subunits p110α and p110β are ubiquitously expressed but differently targeted in tumours. In cancer, PIK3CB (encoding p110β) is seldom mutated compared with PIK3CA (encoding p110α) but can contribute to tumorigenesis in certain PTEN-deficient tumours. The underlying molecular mechanisms are, however, unclear. We have previously reported that p110β is highly expressed in endometrial cancer (EC) cell lines and at the mRNA level in primary patient tumours. Here, we show that p110β protein levels are high in both the cytoplasmic and nuclear compartments in EC cells. Moreover, high nuclear:cytoplasmic staining ratios were detected in high-grade primary tumours. High levels of phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P₃] were measured in the nucleus of EC cells, and pharmacological and genetic approaches showed that its production was partly dependent upon p110β activity. Using immunofluorescence staining, p110β and PtdIns(3,4,5)P₃ were localised in the nucleolus, which correlated with high levels of 47S pre-rRNA. p110β inhibition led to a decrease in both 47S rRNA levels and cell proliferation. In conclusion, these results present a nucleolar role for p110β that may contribute to tumorigenesis in EC.

This article has an associated First Person interview with Fatemeh Mazloumi Gavgani, joint first author of the paper.

I 类磷酸肌醇 3-激酶 (PI3K) 催化亚基 p110α 和 p110β 在肿瘤中普遍表达，但靶向不同。在癌症中，与PIK3CA （编码 p110α）相比， PIK3CB（编码 p110β）很少发生突变，但可以在某些 PTEN 缺陷型肿瘤中促成肿瘤发生。然而，潜在的分子机制尚不清楚。我们之前报道过 p110β 在子宫内膜癌 (EC) 细胞系和原发性患者肿瘤的 mRNA 水平上高度表达。在这里，我们显示 p110β 蛋白水平在 EC 细胞的细胞质和核区室中都很高。此外，在高级别原发性肿瘤中检测到高核：细胞质染色比。高水平的磷脂酰肌醇 (3,4,5)-三磷酸 [PtdIns(3,4,5)P ₃ ] 在 EC 细胞的细胞核中进行了测量，药理学和遗传学方法表明其产生部分依赖于 p110β 活性。使用免疫荧光染色，p110β 和 PtdIns(3,4,5) P ₃定位在核仁中，这与高水平的 47S pre-rRNA 相关。p110β 抑制导致 47S rRNA 水平和细胞增殖均下降。总之，这些结果表明 p110β 的核仁作用可能有助于 EC 中的肿瘤发生。

本文与该论文的联合第一作者 Fatemeh Mazloumi Gavgani 进行了相关的第一人称采访。