title: Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis.
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.
authors.affiliation: State Key Laboratory of Oncology in South China, Departments of Pathology and Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Xin-Jian
authors.initials: XJ
authors.lastname: Li
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Xiang
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Aikseng
authors.initials: A
authors.lastname: Ooi
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Peng
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Lu
authors.forename: Zhongfa
authors.initials: Z
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Petillo
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Ying-Na
authors.initials: YN
authors.lastname: Bao
authors.forename: Fang-Jing
authors.initials: FJ
authors.lastname: Zheng
authors.forename: Claramae Shulyn
authors.initials: CS
authors.lastname: Chia
authors.forename: N Gopalakrishna
authors.initials: NG
authors.lastname: Iyer
authors.forename: Tie-Bang
authors.initials: TB
authors.lastname: Kang
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
chemical_list: D011509:Proteoglycans; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C075430:serglycin