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Conference Paper: Cyclin D1 in Regulation of Liver Cancer Stem Cells
Title | Cyclin D1 in Regulation of Liver Cancer Stem Cells |
---|---|
Authors | |
Issue Date | 2014 |
Publisher | The International Society for Stem Cell Research (ISSCR). |
Citation | The 12th Annual Meeting of the International Society for Stem Cell Research (ISSCR 2014), Vancouver, Canada, 18-21 June 2014. In the Poster Abstracts, 2014, p. 211, abstract no. T-1113 How to Cite? |
Abstract | Cancer stem cells (CSCs) are capable of self-renewal, multipotency,
in vivo tumorigenicity, and driving metastasis, leading to recurrence
of tumor. Thus, novel therapies capable of eliminating CSCs are
needed. Cyclin D1 is deregulated in many types of cancers. Beyond
being a cell cycle regulator and oncogene, cyclin D1 also promotes
stem cell (SC) self-renewal and induced pluripotent stem cells (iPSCs)
reprogramming efficiency. Yet, the role of cyclin D1 in regulation of
CSC is not well defined. In this study, we investigated potential role of
cyclin D1 in regulation of liver cancer stem cell properties. In cyclin D1
overexpressed two lines of liver cancer cells, anchorage-independent
spherical colony (spheres) formation was enriched. From dissected
single spherical cells, the capacity of the secondary and the third sphere
formation was significantly higher in cyclin D1-expressing liver cancer
cells compared to parental cells, suggesting an enhanced self-renewal
capacity. Cyclin D1 expression conferred liver cancer cells more CSC
and SC properties, shown by the increased CD90+ and EpCAM+ liver
CSC populations and the enhanced expression of SC-associated genes
Nanog, Oct4 and Nodal. At longer culturing time, cyclin D1-expressing
spheres maintained a good spherical morphology, whereas parental
spheres became more differentiated. Interestingly, Smad2/3, a TGF-β
signaling effector, was highly phosphorylated in cyclin D1-expressing
spherical cancer cells compared to spherical cells without cyclin D1.
Application of TGF-β/Smad inhibitor (SB431542) significantly reduced
the CSC sphere formation in cyclin D1-expressing cells but had no
effects on parental cell sphere formation. In addition, Erk inhibitor
(UO126) showed no inhibiting effects, a further proof of the cyclin D1-
mediated activation of Smad2/3. Our preliminary data also indicated
the effects of SB431542 in induction of CSC sphere differentiation
and reduction of tumorigenicity. Thus, TGF-β/Smad inhibitor might
have therapeutic potential for targeting liver CSCs. Liver cells are known being highly resistance to chemotherapeutic drugs. We further
investigated the sphere formation capacity of cyclin D1-expressing
cells under the treatment of chemotherapeutic agents in combination
with Smad inhibitor and found that there was an sensitised effect in low
dose and synergistic effect in high dose of SB431542. In summary, our
results suggest that cyclin D1 might promote liver CSC proliferation
and self-renewal via activation of TGF-β/Smad signaling pathway, with
underlining mechanism is under investigation. |
Description | Poster Presentation Session: Cancer Cell |
Persistent Identifier | http://hdl.handle.net/10722/198206 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, X | en_US |
dc.contributor.author | Xia, W | en_US |
dc.contributor.author | Tsao, G | en_US |
dc.contributor.author | Poon, RTP | en_US |
dc.date.accessioned | 2014-06-25T02:54:47Z | - |
dc.date.available | 2014-06-25T02:54:47Z | - |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | The 12th Annual Meeting of the International Society for Stem Cell Research (ISSCR 2014), Vancouver, Canada, 18-21 June 2014. In the Poster Abstracts, 2014, p. 211, abstract no. T-1113 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/198206 | - |
dc.description | Poster Presentation | - |
dc.description | Session: Cancer Cell | - |
dc.description.abstract | Cancer stem cells (CSCs) are capable of self-renewal, multipotency, in vivo tumorigenicity, and driving metastasis, leading to recurrence of tumor. Thus, novel therapies capable of eliminating CSCs are needed. Cyclin D1 is deregulated in many types of cancers. Beyond being a cell cycle regulator and oncogene, cyclin D1 also promotes stem cell (SC) self-renewal and induced pluripotent stem cells (iPSCs) reprogramming efficiency. Yet, the role of cyclin D1 in regulation of CSC is not well defined. In this study, we investigated potential role of cyclin D1 in regulation of liver cancer stem cell properties. In cyclin D1 overexpressed two lines of liver cancer cells, anchorage-independent spherical colony (spheres) formation was enriched. From dissected single spherical cells, the capacity of the secondary and the third sphere formation was significantly higher in cyclin D1-expressing liver cancer cells compared to parental cells, suggesting an enhanced self-renewal capacity. Cyclin D1 expression conferred liver cancer cells more CSC and SC properties, shown by the increased CD90+ and EpCAM+ liver CSC populations and the enhanced expression of SC-associated genes Nanog, Oct4 and Nodal. At longer culturing time, cyclin D1-expressing spheres maintained a good spherical morphology, whereas parental spheres became more differentiated. Interestingly, Smad2/3, a TGF-β signaling effector, was highly phosphorylated in cyclin D1-expressing spherical cancer cells compared to spherical cells without cyclin D1. Application of TGF-β/Smad inhibitor (SB431542) significantly reduced the CSC sphere formation in cyclin D1-expressing cells but had no effects on parental cell sphere formation. In addition, Erk inhibitor (UO126) showed no inhibiting effects, a further proof of the cyclin D1- mediated activation of Smad2/3. Our preliminary data also indicated the effects of SB431542 in induction of CSC sphere differentiation and reduction of tumorigenicity. Thus, TGF-β/Smad inhibitor might have therapeutic potential for targeting liver CSCs. Liver cells are known being highly resistance to chemotherapeutic drugs. We further investigated the sphere formation capacity of cyclin D1-expressing cells under the treatment of chemotherapeutic agents in combination with Smad inhibitor and found that there was an sensitised effect in low dose and synergistic effect in high dose of SB431542. In summary, our results suggest that cyclin D1 might promote liver CSC proliferation and self-renewal via activation of TGF-β/Smad signaling pathway, with underlining mechanism is under investigation. | - |
dc.language | eng | en_US |
dc.publisher | The International Society for Stem Cell Research (ISSCR). | - |
dc.relation.ispartof | Annual Meeting of the International Society for Stem Cell Research, ISSCR 2014 | en_US |
dc.title | Cyclin D1 in Regulation of Liver Cancer Stem Cells | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Wang, X: xqwang@hku.hk | en_US |
dc.identifier.email | Poon, RTP: poontp@hku.hk | en_US |
dc.identifier.authority | Wang, X=rp00507 | en_US |
dc.identifier.authority | Poon, RTP=rp00446 | en_US |
dc.identifier.hkuros | 229548 | en_US |
dc.identifier.spage | 211, abstract no. T-1113 | - |
dc.identifier.epage | 211, abstract no. T-1113 | - |
dc.publisher.place | United States | - |