File Download
There are no files associated with this item.
Supplementary
-
Citations:
- Appears in Collections:
Conference Paper: Serglycin promotes migration and invasion of esophageal cancer cells
Title | Serglycin promotes migration and invasion of esophageal cancer cells |
---|---|
Authors | |
Issue Date | 2019 |
Citation | 2019 Hong Kong Inter-University Postgraduate Symposium in Biochemical Sciences, Hong Kong, 8 June 2019 How to Cite? |
Abstract | Esophageal cancer, of which esophageal squamous cell carcinoma (ESCC) is the major subtype, ranks
sixth in mortality rate among cancer diseases. The prognosis of esophageal cancer is greatly
dependent on the extent of local invasion and metastasis. Therefore, a better understanding of the
molecular mechanisms underlying these processes is needed to identify novel prognostic markers and
therapeutic targets. Our previous study showed that SRGN (encoding serglycin) is the top upregulated
gene in a highly invasive ESCC cell subline. The significance of serglycin, which is a proteoglycan
with a core protein containing an attachment region for glycosaminoglycan (GAG) side chains, in
esophageal cancer is not well understood. In the current study, analysis of TCGA database revealed
that the tumor mRNA expression of SRGN was up-regulated in patients with esophageal cancer, and
that higher SRGN expression was associated with unfavorable prognosis. Analysis of serum samples
from patients showed that higher serum concentration of SRGN was significantly correlated with poor
prognosis, indicating the significant clinical relevance of SRGN in ESCC patients. Our in vitro and in
vivo data showed that SRGN has functional significance in promoting invasion and migration of
ESCC cells. We found that up-regulation of SRGN increased the invasiveness and metastatic potential
of ESCC cells. These effects were due to activation of the ERK signaling pathway, and were
dependent on the integrity of GAG chains attached to the core protein of SRGN. Furthermore,
conditioned medium collected from SRGN-overexpressing cells promoted invasion of parental cells.
This autocrine effect was partly attributed to SRGN-induced midkine (MDK). We found that MDK
has the ability to bind to SRGN, possibly by interacting with its GAG side chains. Up-regulation of
SRGN increased the inhibitory effects of MDK inhibitor on ESCC cell viability. Taken together, our
findings unveiled the functional significance and mechanism of SRGN in promoting ESCC invasion
and metastasis, as well as identified a promising prognostic marker for ESCC patients. [This study is
supported by Research Grants Council of the Hong Kong SAR, China, GRF Project No. 17111016] |
Description | Jointly organized by The Chinese University of Hong Kong (CUHK), The University of Hong Kong (HKU) and The Hong Kong University of Science and Technology (HKUST) poster presentation |
Persistent Identifier | http://hdl.handle.net/10722/272744 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhu, Y | - |
dc.contributor.author | Cheung, A | - |
dc.date.accessioned | 2019-08-06T09:15:45Z | - |
dc.date.available | 2019-08-06T09:15:45Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | 2019 Hong Kong Inter-University Postgraduate Symposium in Biochemical Sciences, Hong Kong, 8 June 2019 | - |
dc.identifier.uri | http://hdl.handle.net/10722/272744 | - |
dc.description | Jointly organized by The Chinese University of Hong Kong (CUHK), The University of Hong Kong (HKU) and The Hong Kong University of Science and Technology (HKUST) | - |
dc.description | poster presentation | - |
dc.description.abstract | Esophageal cancer, of which esophageal squamous cell carcinoma (ESCC) is the major subtype, ranks sixth in mortality rate among cancer diseases. The prognosis of esophageal cancer is greatly dependent on the extent of local invasion and metastasis. Therefore, a better understanding of the molecular mechanisms underlying these processes is needed to identify novel prognostic markers and therapeutic targets. Our previous study showed that SRGN (encoding serglycin) is the top upregulated gene in a highly invasive ESCC cell subline. The significance of serglycin, which is a proteoglycan with a core protein containing an attachment region for glycosaminoglycan (GAG) side chains, in esophageal cancer is not well understood. In the current study, analysis of TCGA database revealed that the tumor mRNA expression of SRGN was up-regulated in patients with esophageal cancer, and that higher SRGN expression was associated with unfavorable prognosis. Analysis of serum samples from patients showed that higher serum concentration of SRGN was significantly correlated with poor prognosis, indicating the significant clinical relevance of SRGN in ESCC patients. Our in vitro and in vivo data showed that SRGN has functional significance in promoting invasion and migration of ESCC cells. We found that up-regulation of SRGN increased the invasiveness and metastatic potential of ESCC cells. These effects were due to activation of the ERK signaling pathway, and were dependent on the integrity of GAG chains attached to the core protein of SRGN. Furthermore, conditioned medium collected from SRGN-overexpressing cells promoted invasion of parental cells. This autocrine effect was partly attributed to SRGN-induced midkine (MDK). We found that MDK has the ability to bind to SRGN, possibly by interacting with its GAG side chains. Up-regulation of SRGN increased the inhibitory effects of MDK inhibitor on ESCC cell viability. Taken together, our findings unveiled the functional significance and mechanism of SRGN in promoting ESCC invasion and metastasis, as well as identified a promising prognostic marker for ESCC patients. [This study is supported by Research Grants Council of the Hong Kong SAR, China, GRF Project No. 17111016] | - |
dc.language | eng | - |
dc.relation.ispartof | Hong Kong Inter-University Postgraduate Symposium in Biochemical Sciences, 2019 | - |
dc.title | Serglycin promotes migration and invasion of esophageal cancer cells | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Cheung, A: lmcheung@hku.hk | - |
dc.identifier.authority | Cheung, A=rp00332 | - |
dc.identifier.hkuros | 300302 | - |