Loss of Hyaluronan and Proteoglycan Link Protein-1 Induces Tumorigenesis in Colorectal Cancer

Wang, Y; Xu, X; Marshall, JE; Gong, M; Zhao, Y; Dua, K; Hansbro, PM; Xu, J; Liu, G

Loss of Hyaluronan and Proteoglycan Link Protein-1 Induces Tumorigenesis in Colorectal Cancer

Wang, Y Xu, X Marshall, JE Gong, M Zhao, Y Dua, K

Hansbro, PM Xu, J Liu, G

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Publisher:: Frontiers Media SA
Publication Type:: Journal Article
Citation:: Frontiers in Oncology, 11

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Field	Value	Language
dc.contributor.author	Wang, Y
dc.contributor.author	Xu, X
dc.contributor.author	Marshall, JE
dc.contributor.author	Gong, M
dc.contributor.author	Zhao, Y
dc.contributor.author	Dua, K https://orcid.org/0000-0002-7507-1159
dc.contributor.author	Hansbro, PM
dc.contributor.author	Xu, J
dc.contributor.author	Liu, G
dc.date.accessioned	2021-12-14T03:51:41Z
dc.date.available	2021-12-14T03:51:41Z
dc.identifier.citation	Frontiers in Oncology, 11
dc.identifier.issn	2234-943X
dc.identifier.uri	http://hdl.handle.net/10453/152312
dc.description.abstract	<jats:p>Colorectal cancer (CRC) is the third most common diagnosed cancer worldwide, but there are no effective cures for it. Hyaluronan and proteoglycan link protein-1 (HAPLN1) is a component of the extracellular matrix (ECM) proteins and involved in the tumor environment in the colon. Transforming growth factor (TGF)-β is a key cytokine that regulates the deposition of ECM proteins in CRC. However, the role of HAPLN1 in TGF-β contributions to CRC remains unknown. We found that the mRNA expression of <jats:italic>HAPLN1</jats:italic> was decreased in tumors from CRC patients compared with healthy controls and normal tissue adjacent to the tumor using two existing microarray datasets. This was validated at the protein level by tissue array from CRC patients (<jats:italic>n</jats:italic> = 59). HAPLN1 protein levels were also reduced in human CRC epithelial cells after 24 h of TGF-β stimulation, and its protein expression correlated with type I collagen alpha-1 (COL1A1) in CRC. Transfection of <jats:italic>HAPLN1</jats:italic> overexpression plasmids into these cells increased protein levels but reduced COL1A1 protein, tumor growth, and cancer cell migration. TGF-β stimulation increased Smad2/3, p-Smad2/3, Smad4, and E-adhesion proteins; however, <jats:italic>HAPLN1</jats:italic> overexpression restored these proteins to baseline levels in CRC epithelial cells after TGF-β stimulation. These findings suggest that HAPLN1 regulates the TGF-β signaling pathway to control collagen deposition <jats:italic>via</jats:italic> the TGF-β signaling pathway and mediates E-adhesion to control tumor growth. Thus, treatments that increase HAPLN1 levels may be a novel therapeutic option for CRC.</jats:p>
dc.language	en
dc.publisher	Frontiers Media SA
dc.relation.ispartof	Frontiers in Oncology
dc.relation.isbasedon	10.3389/fonc.2021.754240
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.title	Loss of Hyaluronan and Proteoglycan Link Protein-1 Induces Tumorigenesis in Colorectal Cancer
dc.type	Journal Article
utslib.citation.volume	11
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy
utslib.copyright.status	open_access	*
dc.date.updated	2021-12-14T03:51:36Z
pubs.publication-status	Published online
pubs.volume	11

Abstract:

Colorectal cancer (CRC) is the third most common diagnosed cancer worldwide, but there are no effective cures for it. Hyaluronan and proteoglycan link protein-1 (HAPLN1) is a component of the extracellular matrix (ECM) proteins and involved in the tumor environment in the colon. Transforming growth factor (TGF)-β is a key cytokine that regulates the deposition of ECM proteins in CRC. However, the role of HAPLN1 in TGF-β contributions to CRC remains unknown. We found that the mRNA expression of HAPLN1 was decreased in tumors from CRC patients compared with healthy controls and normal tissue adjacent to the tumor using two existing microarray datasets. This was validated at the protein level by tissue array from CRC patients (n = 59). HAPLN1 protein levels were also reduced in human CRC epithelial cells after 24 h of TGF-β stimulation, and its protein expression correlated with type I collagen alpha-1 (COL1A1) in CRC. Transfection of HAPLN1 overexpression plasmids into these cells increased protein levels but reduced COL1A1 protein, tumor growth, and cancer cell migration. TGF-β stimulation increased Smad2/3, p-Smad2/3, Smad4, and E-adhesion proteins; however, HAPLN1 overexpression restored these proteins to baseline levels in CRC epithelial cells after TGF-β stimulation. These findings suggest that HAPLN1 regulates the TGF-β signaling pathway to control collagen deposition via the TGF-β signaling pathway and mediates E-adhesion to control tumor growth. Thus, treatments that increase HAPLN1 levels may be a novel therapeutic option for CRC.

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http://hdl.handle.net/10453/152312