Theranostics 2017; 7(1):67-80. doi:10.7150/thno.16752

Research Paper

CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer

Chong Li1,2,7*, Shengwu Liu3,5*, Ruping Yan4*, Ning Han6, Kwok-Kin Wong3,5, Lei Li1,✉

1. Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
2. Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
3. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
4. Department of Urology, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China.
5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
6. Department of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
7. Beijing Jianlan Institute of Medicine, Beijing 100190, China.
* contributed equally to this work.

Abstract

Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. Additional in vitro and in vivo assays showed that CD54 played a critical role in the self-renewal and tumorigenesis of prostate CSCs. Moreover, silencing CD54 greatly reduced the tumorigenesis of prostate cancers both in vitro and in vivo and significantly extended the survival time of tumor-bearing mice in a prostate cancer xenograft model. Dissection of the molecular mechanism revealed that the p38-Notch1 axis was the main downstream signaling pathway in CD54-mediated regulation of CSCs in prostate cancers. Together, these results established that CD54 could be a novel reliable prostate CSC marker and provided a new potential therapeutic target in prostate cancer via CD54-Notch1 signaling.

Keywords: prostate cancer, CD54, cancer stem cells, NOTCH1.

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How to cite this article:
Li C, Liu S, Yan R, Han N, Wong KK, Li L. CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer. Theranostics 2017; 7(1):67-80. doi:10.7150/thno.16752. Available from http://www.thno.org/v07p0067.htm