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

TitleSignificance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
Authors
KeywordsSerglycin
midkine
esophageal squamous cell carcinoma
metastasis
biomarker
Issue Date2021
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/
Citation
Theranostics, 2021, v. 11 n. 6, p. 2722-2741 How to Cite?
AbstractRationale: 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). Methods: Reverse phase protein array analysis was used to identify activated signaling pathways in SRGN-overexpressing cells. Chemokine array was used to identify differentially secreted factors from SRGN-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. Results: In vitro and in vivo experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases. SRGN-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 Delta di-4S and Delta di-6S CS. Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival. Conclusions: 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.
Persistent Identifierhttp://hdl.handle.net/10722/295897
ISSN
2023 Impact Factor: 12.4
2023 SCImago Journal Rankings: 2.912
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, Y-
dc.contributor.authorLau, AKY-
dc.contributor.authorShum, DKY-
dc.contributor.authorCui, D-
dc.contributor.authorZhang, J-
dc.contributor.authorYan, DD-
dc.contributor.authorLi, B-
dc.contributor.authorXu, WW-
dc.contributor.authorLee, NPY-
dc.contributor.authorChan, KT-
dc.contributor.authorLaw, S-
dc.contributor.authorTsao, SW-
dc.contributor.authorCheung, ALM-
dc.date.accessioned2021-02-08T08:15:35Z-
dc.date.available2021-02-08T08:15:35Z-
dc.date.issued2021-
dc.identifier.citationTheranostics, 2021, v. 11 n. 6, p. 2722-2741-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10722/295897-
dc.description.abstractRationale: 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). Methods: Reverse phase protein array analysis was used to identify activated signaling pathways in SRGN-overexpressing cells. Chemokine array was used to identify differentially secreted factors from SRGN-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. Results: In vitro and in vivo experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases. SRGN-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 Delta di-4S and Delta di-6S CS. Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival. Conclusions: 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.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/-
dc.relation.ispartofTheranostics-
dc.rightsTheranostics. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSerglycin-
dc.subjectmidkine-
dc.subjectesophageal squamous cell carcinoma-
dc.subjectmetastasis-
dc.subjectbiomarker-
dc.titleSignificance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer-
dc.typeArticle-
dc.identifier.emailZhu, Y: annayzhu@HKUCC-COM.hku.hk-
dc.identifier.emailShum, DKY: shumdkhk@hkucc.hku.hk-
dc.identifier.emailCui, D: cuidi@HKUCC-COM.hku.hk-
dc.identifier.emailLee, NPY: nikkilee@hku.hk-
dc.identifier.emailChan, KT: ktchan66@hku.hk-
dc.identifier.emailLaw, S: slaw@hku.hk-
dc.identifier.emailTsao, SW: gswtsao@hku.hk-
dc.identifier.emailCheung, ALM: lmcheung@hku.hk-
dc.identifier.authorityShum, DKY=rp00321-
dc.identifier.authorityLee, NPY=rp00263-
dc.identifier.authorityLaw, S=rp00437-
dc.identifier.authorityTsao, SW=rp00399-
dc.identifier.authorityCheung, ALM=rp00332-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/thno.49547-
dc.identifier.pmid33456569-
dc.identifier.pmcidPMC7806492-
dc.identifier.scopuseid_2-s2.0-85100128038-
dc.identifier.hkuros321213-
dc.identifier.volume11-
dc.identifier.issue6-
dc.identifier.spage2722-
dc.identifier.epage2741-
dc.identifier.isiWOS:000604981700015-
dc.publisher.placeAustralia-

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