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CD51 correlates with the TGF-beta pathway and is a functional marker for colorectal cancer stem cells

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Abstract

Colorectal cancer (CRC) is one of the top three most prevalent and deadly cancers. A cancer stem cell (CSC) sub-population that is characterized by the abilities of tumor initiation, self-renewal, metastasis and resistance to chemotherapy can suggest new therapeutic targets. However, no such sub-population has been conclusively identified for CRC, and we lack any marker to identify cells with all of the above characteristics. Here, we report that CD51+ CRC cells displayed greater sphere-forming and tumorigenic capacities, increased migratory and invasive potentials, and enhanced chemoresistance compared with CD51− CRC cells. CD51 knockdown reduced the side population, sphere formation, cell motility and inhibited tumor incidence and metastasis in an in vivo tumor model. Furthermore, CD51 could bind transforming growth factor beta (TGF-β) receptors, and that it upregulated TGF-β/Smad signaling. These results indicate that CD51 is a novel functional marker for colorectal CSCs which may provide an therapeutic target for the efficient elimination of colorectal CSCs.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2012CBA01302); the National Natural Science Foundation of China (81425016, 81270646); the Natural Science Foundation of Guangdong Province (S2013030013305, S20120011190, 2015A030312013); the Key Scientific and Technological Projects of Guangdong Province (2014B020226002, 2015B020226004, 2014B020228003, 2015B020228001); Key Scientific and Technological Program of Guangzhou City (201400000003-3, 201508020262, 201300000089); Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2013).

Author contributions

JW, BZ, HW, JC, XS, YW, HL, WS and APX designed and performed experiments. HW analyzed results. JW, BZ, HW, WS and APX assembled results and wrote the paper. TW, ZC and YQ provided tools, patient specimens and edited the manuscript. All authors participated in critical revision of the manuscript for important intellectual content.

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  1. J Wang, B Zhang and H Wu: These authors contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    J Wang, B Zhang, H Wu, H Xia & A P Xiang

  2. Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China

    J Wang, B Zhang, H Wu, J Cai, Y Wang, H Li, Y Qiu, T Wang & A P Xiang

  3. The Biotherapy Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    J Cai & A P Xiang

  4. Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, China

    X Sui & Q Zhu

  5. Department of Gastrointestinal-Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    Z Chen & W Song

  6. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    A P Xiang

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  1. J Wang
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Wang, J., Zhang, B., Wu, H. et al. CD51 correlates with the TGF-beta pathway and is a functional marker for colorectal cancer stem cells. Oncogene 36, 1351–1363 (2017). https://doi.org/10.1038/onc.2016.299

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