Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer

: Little is known about the roles of proteoglycans in esophageal cancer. This study aims to investigate the roles and mechanisms of serglycin (SRGN) proteoglycan in promoting metastasis of esophageal squamous cell carcinoma (ESCC). : Reverse phase protein array analysis was used to identify activate...

Full description

Saved in:
Bibliographic Details
Published in:Theranostics 2021, Vol.11 (6), p.2722-2741
Main Authors: Zhu, Yun, Lam, Alfred K Y, Shum, Daisy K Y, Cui, Di, Zhang, Jun, Yan, Dong Dong, Li, Bin, Xu, Wen Wen, Lee, Nikki P Y, Chan, Kin Tak, Law, Simon, Tsao, Sai Wah, Cheung, Annie L M
Format: Article
Language:English
Subjects:
Animals
Antibodies
Apoptosis
Autocrine Communication - physiology
Biomarkers, Tumor - metabolism
Biotechnology
Carcinogenesis - metabolism
Carcinogenesis - pathology
Cell Line, Tumor
Cell Movement - physiology
Esophageal cancer
Esophageal Neoplasms - metabolism
Esophageal Neoplasms - pathology
Esophageal Squamous Cell Carcinoma - metabolism
Esophageal Squamous Cell Carcinoma - pathology
Female
Gene Expression Regulation, Neoplastic - physiology
Humans
Hyaluronan Receptors - metabolism
Male
Matrix Metalloproteinase 2 - metabolism
Metastasis
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Midkine - metabolism
Mortality
Peptides
Phosphatase
Prognosis
Proteins
Proteoglycans - metabolism
Proto-Oncogene Proteins c-myc - metabolism
Research Paper
Signal Transduction - physiology
Squamous cell carcinoma
Up-Regulation - physiology
Vesicular Transport Proteins - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:: Little is known about the roles of proteoglycans in esophageal cancer. This study aims to investigate the roles and mechanisms of serglycin (SRGN) proteoglycan in promoting metastasis of esophageal squamous cell carcinoma (ESCC). : Reverse phase protein array analysis was used to identify activated signaling pathways in -overexpressing cells. Chemokine array was used to identify differentially secreted factors from -overexpressing cells. Binding between SRGN and potential interacting partners was evaluated using proximity ligation assay and co-immunoprecipitation. The glycosaminoglycan (GAG) chains of SRGN were characterized using fluorophore-assisted carbohydrate electrophoresis. Tissue microarray and serum samples were used to determine the correlation of SRGN expression with clinicopathological parameters and patient survival. : and experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases. -knockdown suppressed tumorigenic hallmarks. These SRGN-elicited functions were carried out in an autocrine manner by inducing the secretion of midkine (MDK), which was further identified as a novel binding partner of SRGN for the formation of a SRGN/MDK/CD44 complex. In addition, SRGN interacted with MDK and matrix metalloproteinase 2 in ESCC via its GAG chains, which were mainly decorated with chondroitin sulfate comprising of ∆di-4S and ∆di-6S CS. Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival. : This study provides the first evidence that elevated serum SRGN has prognostic significance in patients with ESCC, and sheds light on the molecular mechanism by which elevated circulating SRGN in cancer patients might promote cancer progression.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.49547