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Ski modulate the characteristics of pancreatic cancer stem cells via regulating sonic hedgehog signaling pathway

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Tumor Biology

Abstract

Evidence from in vitro and in vivo studies shows that Ski may act as both a tumor proliferation-promoting factor and a metastatic suppressor in human pancreatic cancer and also may be a therapeutic target of integrative therapies. At present, pancreatic cancer stem cells (CSCs) are responsible for tumor recurrence accompanied by resistance to conventional therapies. Sonic hedgehog (Shh) signaling pathway is found to be aberrantly activated in CSCs. The objectives of this study were to investigate the role of Ski in modulating pancreatic CSCs and to examine the molecular mechanisms involved in pancreatic cancer treatment both in vivo and in vitro. In in vitro study, the results showed that enhanced Ski expression could increase the expression of pluripotency maintaining markers, such as CD24, CD44, Sox-2, and Oct-4, and also components of Shh signaling pathway, such as Shh, Ptch-1, Smo, Gli-1, and Gli-2, whereas depletion of Ski to the contrary. Then, we investigated the underlying mechanism and found that inhibiting Gli-2 expression by short interfering RNA (siRNA) can decrease the effects of Ski on the maintenance of pancreatic CSCs, indicating that Ski mediates the pluripotency of pancreatic CSCs mainly through Shh pathway. The conclusion is that Ski may be an important factor in maintaining the stemness of pancreatic CSCs through modulating Shh pathway.

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Acknowledgments

We thank Te Liu (Shanghai Geriatric Institute of Chinese Medicine, Shanghai) for experimental and technical help.

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Authors and Affiliations

  1. Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

    Libin Song, Song Gao, Chenyue Zhang, Chao Qu, Peng Wang & Luming Liu

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Libin Song, Song Gao, Chenyue Zhang, Chao Qu, Peng Wang & Luming Liu

  3. Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China

    Xiangyuan Chen

  4. Department of Anaesthesiology, Shanghai Medical College, Fudan University, Shanghai, China

    Xiangyuan Chen

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  1. Libin Song
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  2. Xiangyuan Chen
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  3. Song Gao
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  4. Chenyue Zhang
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  5. Chao Qu
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  6. Peng Wang
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  7. Luming Liu
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Correspondence to Luming Liu.

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Libin Song and Xiangyuan Chen contributed to the work equally.

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Song, L., Chen, X., Gao, S. et al. Ski modulate the characteristics of pancreatic cancer stem cells via regulating sonic hedgehog signaling pathway. Tumor Biol. 37, 16115–16125 (2016). https://doi.org/10.1007/s13277-016-5461-8

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