WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Bisson, Isabelle; Prowse, David M.

doi:10.1038/cr.2009.43

Cited by 264 publications

(218 citation statements)

References 72 publications

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“…9B). We further confirmed the role of Sur8 in maintenance of self-renewal by adapting the single-cell clonal assay, which provide better results than the traditional neurosphere assay [16]. The neurospheres which were formed from single cells were reduced in size around 40% by infection of Sur8 knockdown lentivirus (Fig.…”

Section: Sur8 Plays a Role In Inhibiting Npc Differentiationsupporting

confidence: 63%

“…The neurosphere cells were dissociated with 0.25% trypsin-EDTA (Invitrogen, Grand Island, NY, http://www.invitrogen.com) for the purpose of immunocytochemistry analyses. For single-cell clonal assay [16], we serially diluted cell suspensions into each well of 96-well plates. We marked wells containing single cell after microscopic confirmation and analyzed neurospheres up to the third passage.…”

Section: Preparation and Culture Of Neuronal Progenitor Cells And Neumentioning

confidence: 99%

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Sur8/Shoc2 Involves Both Inhibition of Differentiation and Maintenance of Self-Renewal of Neural Progenitor Cells via Modulation of Extracellular Signal-Regulated Kinase Signaling

Moon

Kim

et al. 2011

Stem Cells

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Sur8/Shoc2 is a scaffold protein that regulates the Rasextracellular signal-regulated kinase (ERK) pathway. However, the roles of Sur8 in cellular physiologies are poorly understood. In this study, Sur8 was severely repressed in the course of neural progenitor cell (NPC) differentiation in the cerebral cortex of developing rat embryos. Similarly, Sur8 was also critically reduced in cultured NPCs, which were induced differentiation by removal of basic fibroblast growth factor (bFGF). Sur8 regulation occurs at the protein level rather than at the mRNA level as revealed by both in situ hybridization and reverse transcriptase polymerase chain reaction analyses. The role of Sur8 in NPC differentiation was confirmed by lentivirus-mediated Sur8 knockdown, which resulted in increased differentiation, whereas exogenous expression of Sur8 inhibited differentiation. Contrastingly, NPC proliferation was promoted by overexpression, but was suppressed by Sur8 knockdown. The role of Sur8 as an antidifferentiation factor in the developing rat brain was confirmed by an ex vivo embryo culture system combined with the lentivirus-mediated Sur8 knockdown. The numbers and sizes of neurospheres were reduced, but neuronal outgrowth was enhanced by the Sur8 knockdown. The Ras-ERK pathway is involved in Sur8-mediated regulations of differentiation, as the treatment of ERK kinase (MEK) inhibitors blocks the effects of Sur8. The regulations of NPCs' differentiation and proliferation by the Ras-ERK pathway were also shown by the rescues of the effects of bFGF depletion, neuronal differentiation, and antiproliferation by epidermal growth factor. In summary, Sur8 is an antidifferentiation factor that stimulates proliferation for maintenance of self-renewal in NPCs via modulation of the Ras-ERK pathway. STEM CELLS 2011; 29:320-331 Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Sur8 Plays a Role In Inhibiting Npc Differentiationsupporting

confidence: 63%

Section: Preparation and Culture Of Neuronal Progenitor Cells And Neumentioning

confidence: 99%

Sur8/Shoc2 Involves Both Inhibition of Differentiation and Maintenance of Self-Renewal of Neural Progenitor Cells via Modulation of Extracellular Signal-Regulated Kinase Signaling

Moon

Kim

et al. 2011

Stem Cells

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“…9,29,30 To confirm that c-T3 treatment can inhibit prostate CSC properties, prostasphere formation of PC-3 cells was studied in the presence or absence of c-T3. As shown in Figure 3a, after culturing the cells for 14 days in nonadherent condition, an average of 21 prostaspheres per well were found in the untreated group.…”

Section: C-t3 Inhibits Prostasphere Formation Of Pc-3 Cells Under Nonmentioning

confidence: 99%

Gamma‐tocotrienol as an effective agent in targeting prostate cancer stem cell‐like population

Luk

Yap²,

Chiu

et al. 2011

Intl Journal of Cancer

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Emerging evidence supports that prostate cancer originates from a rare subpopulation of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma‐tocotrienols (γ‐T3) is one of the vitamin‐E constituents, which have been shown to have anticancer effects against a wide range of human cancers. Recently, we have reported that γ‐T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel‐induced apoptosis, suggesting that γ‐T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that γ‐T3 can downregulate the expression of prostate CSC markers (CD133/CD44) in androgen‐independent prostate cancer cell lines (PC‐3 and DU145), as evident from Western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by γ‐T3 treatment. In addition, pretreatment of PC‐3 cells with γ‐T3 was found to suppress tumor initiation ability of the cells. More importantly, although CD133‐enriched PC‐3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to γ‐T3 treatment as the CD133‐depleted population. Our data suggest that γ‐T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.

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“…The similarities between normal adult stem cells and CSCs suggest that the signaling pathways involved in somatic stem cell maintenance may also be involved in the regulation of CSCs. This assumption is verified in certain CSCs, such as colon (15), prostate (16) and cutaneous cancer (17), chronic myeloid leukemia (18), acute myelogenous leukemia (19) and hepatic carcinoma (20). The Wnt signaling pathway is a highly conserved signaling pathway.…”

Section: Introductionmentioning

confidence: 91%

The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer

Cai

Zhu

2012

Mol Med Report

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Abstract. Cancer stem cells (CSCs) possess the ability of self-renewal and tumor initiation. Targeting key signaling pathways that are active in CSC self-renewal is one approach to cancer therapy. Abnormal activation of the Wnt/β-catenin pathway has been described in a wide variety of human cancers and in CSCs; however, the role of this pathway in gastric CSCs has not been reported. In our study, we investigated whether the Wnt/β-catenin pathway plays an important role in gastric CSCs. First, we isolated cancer stem-like cells (CSLCs) from the human gastric cancer cell line MKN-45 using tumorsphere cultures. We tested whether tumorsphere cells were CSLCs using the following three criteria: i) We identified that the expression of the CSC marker CD44 was significantly greater in tumorsphere cells compared to adherent cells; ii) compared with adherent cells, the floating tumorsphere cells had greater self-renewing capacity; iii) in vivo xenograft studies showed that tumorsphere cells generate larger tumors than adherent cells at the same number. In addition, we studied the mechanism(s) by which the canonical Wnt signaling pathway acts in CSLCs. Western blotting and real-time PCR showed that the expression levels of β-catenin and c-myc, cyclin d1 and axin 2 were downregulated/upregulated with the inhibition/activation of the Wnt pathway. The pathway blocked by DKK-1 caused a higher reduction in the self-renewing capacity of MKN-45 tumorsphere cells and the pathway activated by lithium chloride improved the self-renewal of CSLCs. In conclusion, our data suggested that the Wnt/β-catenin pathway is essential for the self-renewal of CSLCs in human gastric cancer.

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WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Cited by 264 publications

References 72 publications

Sur8/Shoc2 Involves Both Inhibition of Differentiation and Maintenance of Self-Renewal of Neural Progenitor Cells via Modulation of Extracellular Signal-Regulated Kinase Signaling

Sur8/Shoc2 Involves Both Inhibition of Differentiation and Maintenance of Self-Renewal of Neural Progenitor Cells via Modulation of Extracellular Signal-Regulated Kinase Signaling

Gamma‐tocotrienol as an effective agent in targeting prostate cancer stem cell‐like population

The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer

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