Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis

Xin Jian Li, Choon Kiat Ong, Yun Cao, Yan Qun Xiang, Jian Yong Shao, Aikseng Ooi, Li Xia Peng, Wen Hua Lu, Zhongfa Zhang, David Petillo, Li Qin, Ying Na Bao, Fang Jing Zheng, Claramae Shulyn Chia, N. Gopalakrishna Iyer, Tie Bang Kang, Yi Xin Zeng, Khee Chee Soo, Jeffrey M. Trent, Bin Tean TehChao Nan Qian

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.

Original languageEnglish (US)
Pages (from-to)3162-3172
Number of pages11
JournalCancer Research
Volume71
Issue number8
DOIs
StatePublished - Apr 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Li, X. J., Ong, C. K., Cao, Y., Xiang, Y. Q., Shao, J. Y., Ooi, A., Peng, L. X., Lu, W. H., Zhang, Z., Petillo, D., Qin, L., Bao, Y. N., Zheng, F. J., Chia, C. S., Iyer, N. G., Kang, T. B., Zeng, Y. X., Soo, K. C., Trent, J. M., ... Qian, C. N. (2011). Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis. Cancer Research, 71(8), 3162-3172. https://doi.org/10.1158/0008-5472.CAN-10-3557