Abstract 3168: Serglycin promotes migration and invasion of esophageal cancer cells
Authors: Yun ZHU, Bin Li, Wenwen Xu, Aky Lam, Simon Law, ALM Cheung
Journal: Cancer Research (2018)

Abstract Esophageal cancer is the eighth most common cancer in the world and it ranks sixth in mortality rate among cancer diseases. While patients with early stage esophageal cancer without metastasis have a better chance of being cured by surgery, most patients present with locally advanced or metastatic disease. Unfortunately, some common cancer biomarkers such as carcinoembryonic antigen (CEA) and CA19-9 have low sensitivity and specificity in esophageal cancer. A better understanding of the molecular mechanisms underlying esophageal cancer progression is needed to identify novel diagnostic markers and therapeutic targets for intervention. We previously identified serglycin (SRGN) as the top upregulated gene in a highly invasive esophageal squamous cell carcinoma (ESCC) cell subline. Serglycin is a proteoglycan with a core protein and glycosaminoglycan (GAG) chains. Its significance in tumorigenesis is not well understood. The GAG chains have the ability of binding specific growth factors and ligands, which may play an important role in facilitating cancer cell migration and invasion. Immunohistochemical analysis showed that serglycin expression was higher in ESCC compared with normal esophageal epithelium, and in lymph node metastases compared with primary ESCC. Ectopic overexpression of serglycin in ESCC cells enhanced their migration and invasion potential in vitro. Knockdown of serglycin reduced ESCC cell migration and invasion. In invasion chamber assays, conditioned medium (CM) from SRGN-overexpressing ESCC cells stimulated the migration and invasion ability of less invasive ESCC cells. Conditioned medium from ESCC cells expressing serglycin that lacks the GAG attachment site had no such effects. Chemokine antibody array analysis showed that midkine (MDK), a heparin-binding growth factor, was the top upregulated protein in the CM of SRGN-overexpressing cells. Analysis of TCGA and GTEx datasets showed that MDK expression was higher in many cancer types such as breast cancer, colon adenocarcinoma, glioblastoma and lung cancer, than in corresponding normal tissues. Western blot analysis showed that forced expression of serglycin, but not serglycin without the GAG binding domain, led to increase of MDK in the CM of multiple ESCC cell lines. Forced expression of serglycin also increased the expression level of phosphorylated extracellular signal-regulated kinase (p-ERK) in ESCC cells. Taken together, serglycin may play an important role in the progression ESCC by promoting migration and invasion of cancer cells. These effects may be mediated through activation of the ERK signaling pathway. Whether MDK is involved in this regulatory mechanism warrants further investigation. [This study was supported by Research Grants Council of the Hong Kong SAR, China, GRF Project No. 17111016] Citation Format: Yun ZHU, Bin Li, Wenwen Xu, Aky Lam, Simon Law, ALM Cheung. Serglycin promotes migration and invasion of esophageal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3168.