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Mol. Cells 2013; 36(2): 138-144

Published online August 31, 2013

https://doi.org/10.1007/s10059-013-0096-8

© The Korean Society for Molecular and Cellular Biology

Epithelial-Mesenchymal Transition and Migration of Prostate Cancer Stem Cells Is Driven by Cancer-Associated Fibroblasts in an HIF-1α/β-Catenin-Dependent Pathway

Yong Luo, Ling Lan, Yong-Guang Jiang, Jia-Hui Zhao, Ming-Chuan Li, Neng-Bao Wei, and Yun-Hua Lin

Department of Urology, Affiliated Beijing Anzhen Hospital of Capital Medical University, Beijing, People’s Republic of China, 1Department of Endocrinology, Beijing Jishuitan Hospital, The 4th Clinical Medical College of Peking University, Beijing, People’s Republic of China

Received: March 26, 2013; Revised: May 31, 2013; Accepted: June 3, 2013

Abstract

Although cancer stem cells (CSCs) play a crucial role in seeding the initiation of tumor progression, they do not always possess the same potent ability as tumor metastasis. Thus, precisely how migrating CSCs occur, still remains unclear. In the present study, we first comparatively analyzed a series of prostate CSCs, which exhibited a dynamically increasing and disseminating ability in nude mice. We observed that the transcriptional activity of HIF-1α and β-catenin became gradually elevated in these stem cells and their epithelial-mesenchymal transition (EMT) characteristic altered from an epithelial type to a mesenchymal type. Next, we further used cancer-associated fibroblasts (CAFs), which were cultured from surgically resected tissues of prostate cancer (PCa) to stimulate prostate CSCs. Similar results were reconfirmed and showed that the protein levels of both HIF-1α and β-catenin were markedly improved. In addition, the EMT phenotype displayed a homogenous mesenchymal type, accompanied with increased aggressive potency in vitro. Most importantly, the aforementioned promoting effect of CAFs on prostate CSCs was completely repressed after “silencing” the activity of β-catenin by transfection of stem cells with ShRNA. Taken together, our observations suggest that prostate migrating CSCs, with a mesenchymal phenotype, could be triggered by CAFs in a HIF-1α/β-catenin-dependent signaling pathway.

Keywords cancer-associated fibroblast, epithelial-mesenchymal transition, migrating cancer stem cell, prostate cancer

Article

Research Article

Mol. Cells 2013; 36(2): 138-144

Published online August 31, 2013 https://doi.org/10.1007/s10059-013-0096-8

Copyright © The Korean Society for Molecular and Cellular Biology.

Epithelial-Mesenchymal Transition and Migration of Prostate Cancer Stem Cells Is Driven by Cancer-Associated Fibroblasts in an HIF-1α/β-Catenin-Dependent Pathway

Yong Luo, Ling Lan, Yong-Guang Jiang, Jia-Hui Zhao, Ming-Chuan Li, Neng-Bao Wei, and Yun-Hua Lin

Department of Urology, Affiliated Beijing Anzhen Hospital of Capital Medical University, Beijing, People’s Republic of China, 1Department of Endocrinology, Beijing Jishuitan Hospital, The 4th Clinical Medical College of Peking University, Beijing, People’s Republic of China

Received: March 26, 2013; Revised: May 31, 2013; Accepted: June 3, 2013

Abstract

Although cancer stem cells (CSCs) play a crucial role in seeding the initiation of tumor progression, they do not always possess the same potent ability as tumor metastasis. Thus, precisely how migrating CSCs occur, still remains unclear. In the present study, we first comparatively analyzed a series of prostate CSCs, which exhibited a dynamically increasing and disseminating ability in nude mice. We observed that the transcriptional activity of HIF-1α and β-catenin became gradually elevated in these stem cells and their epithelial-mesenchymal transition (EMT) characteristic altered from an epithelial type to a mesenchymal type. Next, we further used cancer-associated fibroblasts (CAFs), which were cultured from surgically resected tissues of prostate cancer (PCa) to stimulate prostate CSCs. Similar results were reconfirmed and showed that the protein levels of both HIF-1α and β-catenin were markedly improved. In addition, the EMT phenotype displayed a homogenous mesenchymal type, accompanied with increased aggressive potency in vitro. Most importantly, the aforementioned promoting effect of CAFs on prostate CSCs was completely repressed after “silencing” the activity of β-catenin by transfection of stem cells with ShRNA. Taken together, our observations suggest that prostate migrating CSCs, with a mesenchymal phenotype, could be triggered by CAFs in a HIF-1α/β-catenin-dependent signaling pathway.

Keywords: cancer-associated fibroblast, epithelial-mesenchymal transition, migrating cancer stem cell, prostate cancer

Mol. Cells
Dec 31, 2021 Vol.44 No.12, pp. 861~919
COVER PICTURE
Structure of the fly peripheral neurons in the fly head. Flies have basic sensory organs including eyes for vision, antennae and maxillary palps for olfaction, and proboscis (magenta) for gustation which can be labelled with monoclonal antibody 22C10. The figure is a 3D reconstructed image with 30 slices of confocal sections with 3 μm interval. It shows that the proboscis is required for sensing attractive carboxylic acids such as glycolic acid, citric acid, and lactic acid (Shrestha and Lee, pp. 900-910).

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