The Key Laboratory of Molecular Biology, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
Department of Thoracic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Int J Biochem Cell Biol. 2021 Feb;131:105898. doi: 10.1016/j.biocel.2020.105898. Epub 2020 Dec 4.
Abnormal intraglandular stromal-epithelial interactions have been known as a main key contributing factor for development of Benign Prostatic Hyperplasia (BPH). However, the underlying mechanism for the dysregulated intercellular communication remains unclear. In this study we compared the proteomic profiles of hyperplastic tissue with adjacent normal tissue of BPH and identified Rab27B small GTPase, a key regulator of exocytosis, as a protein that was overexpressed in the epithelium of BPH tissue. Overexpression of Rab27B in prostatic epithelial cells strongly increased the signaling activities of the PI3K/AKT and ERK1/2 pathways, whereas, downregulation of Rab27B expression in the epithelial cells of BPH reduced the signaling activities and decreased cell proliferation. The elevated Rab27B expression caused an overall increase in cell surface presentation of growth factor receptors without affecting their expression. However, the small GTPase also possesses an inhibitory activity against mTORC1 independent of its role in cell surface presentation of growth factor receptors. Our findings demonstrate a pivotal role of the small GTPase in autocrine and paracrine signaling and suggest that its abnormal expression underlies the dysregulated stromal-epithelial interactions in BPH.
异常的腺体内基质-上皮相互作用已被认为是良性前列腺增生（BPH）发展的主要关键因素。然而，细胞间通讯失调的潜在机制仍不清楚。在这项研究中，我们比较了 BPH 增生组织和相邻正常组织的蛋白质组图谱，鉴定出 Rab27B 小 GTPase 是一种细胞外泌作用的关键调节因子，在 BPH 组织的上皮细胞中过度表达。Rab27B 在前列腺上皮细胞中的过度表达强烈增加了 PI3K/AKT 和 ERK1/2 途径的信号活性，而在 BPH 上皮细胞中下调 Rab27B 的表达则降低了信号活性并减少了细胞增殖。升高的 Rab27B 表达导致生长因子受体的细胞表面呈现总体增加，而不影响其表达。然而，这种小 GTPase 还具有一种独立于其在生长因子受体细胞表面呈现中的作用的对 mTORC1 的抑制活性。我们的研究结果表明，这种小 GTPase 在自分泌和旁分泌信号中起着关键作用，并表明其异常表达是 BPH 中基质-上皮相互作用失调的基础。
