title: Epithelial-mesenchymal transition and migration of prostate cancer stem cells is driven by cancer-associated fibroblasts in an HIF-1α/β-catenin-dependent pathway.
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.
authors.affiliation: Department of Urology, Affiliated Beijing Anzhen Hospital of Capital Medical University, Beijing, People's Republic of China, luoyonganzhen@163.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.forename: Ling
authors.initials: L
authors.lastname: Lan
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Jiang
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Zhao
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Li
authors.forename: Neng-Bao
authors.initials: NB
authors.lastname: Wei
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Lin
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D051176:beta Catenin