多囊肾病蛋白3定位于晚期内体，以维持Rab7依赖的内溶酶体稳态。

PKD3 localizes to late endosomes to maintain Rab7-dependent endolysosomal homeostasis.

作者信息

Gutiérrez-Galindo Elena, Jursik Katharina, Frey Yannick, Meyer Florian, Hausser Angelika

机构信息

Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.

Institute of Pathophysiology, Medical University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

出版信息

iScience. 2025 Aug 20;28(9):113408. doi: 10.1016/j.isci.2025.113408. eCollection 2025 Sep 19.

DOI:10.1016/j.isci.2025.113408

PMID:40970203

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12441718/

Abstract

Protein kinase D3 (PKD3) is an important regulator of triple-negative breast cancer (TNBC) progression by promoting invasion, proliferation, and stem cell maintenance. However, the mechanism underlying these cellular functions has remained unclear. Here, we report that endogenous PKD3 localizes to Rab7-positive vesicles in MDA-MB-231 cells cultured on stiff matrices. Notably, PKD3 depletion results in smaller Rab7-positive vesicles with reduced retromer complex recruitment, leading to enhanced cathepsin D secretion. This correlates with impaired endosomal acidification, which is associated with dysregulated Wnt signaling and a decline in stemness. Our data thus unveil a previously unrecognized role of PKD3 in regulating endolysosomal dynamics that contributes to the maintenance of the cancer stem cell population in TNBC.

摘要

蛋白激酶D3（PKD3）是三阴性乳腺癌（TNBC）进展的重要调节因子，可促进侵袭、增殖和干细胞维持。然而，这些细胞功能背后的机制仍不清楚。在这里，我们报告内源性PKD3定位于在坚硬基质上培养的MDA-MB-231细胞中的Rab7阳性囊泡。值得注意的是，PKD3缺失导致Rab7阳性囊泡变小，逆向转运复合物募集减少，从而导致组织蛋白酶D分泌增加。这与内体酸化受损相关，内体酸化受损与Wnt信号失调和干性下降有关。因此，我们的数据揭示了PKD3在调节内溶酶体动力学中的一个以前未被认识的作用，这有助于维持TNBC中的癌症干细胞群体。