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WNT/β-连环蛋白指导 hTERT 前列腺癌干细胞的自我更新对称细胞分裂。

WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERT Prostate Cancer Stem Cells.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Cancer Res. 2017 May 1;77(9):2534-2547. doi: 10.1158/0008-5472.CAN-16-1887. Epub 2017 Feb 16.

Abstract

Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here, we report that the hTERT prostate cancer cells exhibit CSC properties, including a stem cell-associated gene expression signature, long-term tumor-propagating capacity and epithelial-to-mesenchymal transition. In promoting the self-renewal symmetric division of hTERT prostate cancer cells, WNT3a dramatically decreased the ratio of hTERT prostate cancer cells undergoing asymmetric division. Increased WNT/β-catenin signal activation was also detected in hTERT prostate cancer cells. hTERT-mediated CSC properties were at least partially dependent on β-catenin. These findings provide novel cellular and molecular mechanisms for the self-renewal of CSC orchestrated by tumor microenvironmental stimuli and intracellular signals. .

摘要

癌症干细胞(CSC)驱动癌症的进展和复发。CSC 的自我更新和扩增是通过对称细胞分裂来实现的,然而,外部刺激如何影响 CSC 分裂模式和干性的细胞内调节程序仍然不清楚。在这里,我们报告 hTERT 前列腺癌细胞表现出 CSC 特性,包括干细胞相关基因表达特征、长期肿瘤传播能力和上皮-间充质转化。在促进 hTERT 前列腺癌细胞的自我更新对称分裂中,WNT3a 显著降低了 hTERT 前列腺癌细胞进行不对称分裂的比例。在 hTERT 前列腺癌细胞中也检测到 WNT/β-catenin 信号的激活增加。hTERT 介导的 CSC 特性至少部分依赖于β-catenin。这些发现为肿瘤微环境刺激和细胞内信号协调的 CSC 自我更新提供了新的细胞和分子机制。

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