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

Rationale: 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 i...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806492/
https://www.ncbi.nlm.nih.gov/pubmed/33456569
http://dx.doi.org/10.7150/thno.49547
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author 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.
author_facet 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.
author_sort Zhu, Yun
collection PubMed
description Rationale: 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 ∆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. 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.
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spelling pubmed-78064922021-01-15 Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer 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. Theranostics Research Paper Rationale: 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 ∆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. 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. Ivyspring International Publisher 2021-01-01 /pmc/articles/PMC7806492/ /pubmed/33456569 http://dx.doi.org/10.7150/thno.49547 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
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.
Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
title Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
title_full Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
title_fullStr Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
title_full_unstemmed Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
title_short Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
title_sort significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806492/
https://www.ncbi.nlm.nih.gov/pubmed/33456569
http://dx.doi.org/10.7150/thno.49547
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