'MCC' protein interacts with E-cadherin and β-catenin strengthening cell-cell adhesion of HCT116 colon cancer cells.

Benthani, FA; Herrmann, D; Tran, PN; Pangon, L; Lucas, MC; Allam, AH; Currey, N; Al-Sohaily, S; Giry-Laterriere, M; Warusavitarne, J; Timpson, P; Kohonen-Corish, MRJ

'MCC' protein interacts with E-cadherin and β-catenin strengthening cell-cell adhesion of HCT116 colon cancer cells.

Benthani, FA Herrmann, D Tran, PN Pangon, L Lucas, MC Allam, AH Currey, N Al-Sohaily, S Giry-Laterriere, M Warusavitarne, J Timpson, P Kohonen-Corish, MRJ

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Publisher:: NATURE PUBLISHING GROUP
Publication Type:: Journal Article
Citation:: Oncogene, 2018, 37, (5), pp. 663-672
Issue Date:: 2018-02-01

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Field	Value	Language
dc.contributor.author	Benthani, FA
dc.contributor.author	Herrmann, D
dc.contributor.author	Tran, PN
dc.contributor.author	Pangon, L
dc.contributor.author	Lucas, MC
dc.contributor.author	Allam, AH
dc.contributor.author	Currey, N
dc.contributor.author	Al-Sohaily, S
dc.contributor.author	Giry-Laterriere, M
dc.contributor.author	Warusavitarne, J
dc.contributor.author	Timpson, P
dc.contributor.author	Kohonen-Corish, MRJ
dc.date.accessioned	2022-09-12T23:06:24Z
dc.date.available	2017-08-25
dc.date.available	2022-09-12T23:06:24Z
dc.date.issued	2018-02-01
dc.identifier.citation	Oncogene, 2018, 37, (5), pp. 663-672
dc.identifier.issn	0950-9232
dc.identifier.issn	1476-5594
dc.identifier.uri	http://hdl.handle.net/10453/161767
dc.description.abstract	E-cadherin and β-catenin are key proteins that are essential in the formation of the epithelial cell layer in the colon but their regulatory pathways that are disrupted in cancer metastasis are not completely understood. Mutated in colorectal cancer (MCC) is a tumour suppressor gene that is silenced by promoter methylation in colorectal cancer and particularly in patients with increased lymph node metastasis. Here, we show that MCC methylation is found in 45% of colon and 24% of rectal cancers and is associated with proximal colon, poorly differentiated, circumferential and mucinous tumours as well as increasing T stage and larger tumour size. Knockdown of MCC in HCT116 colon cancer cells caused a reduction in E-cadherin protein level, which is a hallmark of epithelial-mesenchymal transition in cancer, and consequently diminished the E-cadherin/β-catenin complex. MCC knockdown disrupted cell-cell adhesive strength and integrity in the dispase and transepithelial electrical resistance assays, enhanced hepatocyte growth factor-induced cell scatter and increased tumour cell invasiveness in an organotypic assay. The Src/Abl inhibitor dasatinib, a candidate anti-invasive drug, abrogated the invasive properties induced by MCC deficiency. Mechanistically, we establish that MCC interacts with the E-cadherin/β-catenin complex. These data provide a significant advance in the current understanding of cell-cell adhesion in colon cancer cells.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	NATURE PUBLISHING GROUP
dc.relation	http://purl.org/au-research/grants/nhmrc/1020406
dc.relation.ispartof	Oncogene
dc.relation.isbasedon	10.1038/onc.2017.362
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.subject.mesh	Antigens, CD
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Cadherins
dc.subject.mesh	Cell Adhesion
dc.subject.mesh	Cell Membrane
dc.subject.mesh	Cohort Studies
dc.subject.mesh	Colon
dc.subject.mesh	Colorectal Neoplasms
dc.subject.mesh	DNA Methylation
dc.subject.mesh	Dasatinib
dc.subject.mesh	Epithelial-Mesenchymal Transition
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Gene Knockdown Techniques
dc.subject.mesh	HCT116 Cells
dc.subject.mesh	Humans
dc.subject.mesh	Lymphatic Metastasis
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Neoplasm Staging
dc.subject.mesh	Prognosis
dc.subject.mesh	Promoter Regions, Genetic
dc.subject.mesh	Protein Binding
dc.subject.mesh	Tumor Suppressor Proteins
dc.subject.mesh	beta Catenin
dc.subject.mesh	Colon
dc.subject.mesh	HCT116 Cells
dc.subject.mesh	Cell Membrane
dc.subject.mesh	Humans
dc.subject.mesh	Colorectal Neoplasms
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Lymphatic Metastasis
dc.subject.mesh	Cadherins
dc.subject.mesh	Tumor Suppressor Proteins
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Antigens, CD
dc.subject.mesh	Neoplasm Staging
dc.subject.mesh	Prognosis
dc.subject.mesh	Cohort Studies
dc.subject.mesh	Cell Adhesion
dc.subject.mesh	DNA Methylation
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Protein Binding
dc.subject.mesh	beta Catenin
dc.subject.mesh	Promoter Regions, Genetic
dc.subject.mesh	Gene Knockdown Techniques
dc.subject.mesh	Epithelial-Mesenchymal Transition
dc.subject.mesh	Dasatinib
dc.title	'MCC' protein interacts with E-cadherin and β-catenin strengthening cell-cell adhesion of HCT116 colon cancer cells.
dc.type	Journal Article
utslib.citation.volume	37
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access	*
dc.date.updated	2022-09-12T23:06:23Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	37
utslib.citation.issue	5

Abstract:

E-cadherin and β-catenin are key proteins that are essential in the formation of the epithelial cell layer in the colon but their regulatory pathways that are disrupted in cancer metastasis are not completely understood. Mutated in colorectal cancer (MCC) is a tumour suppressor gene that is silenced by promoter methylation in colorectal cancer and particularly in patients with increased lymph node metastasis. Here, we show that MCC methylation is found in 45% of colon and 24% of rectal cancers and is associated with proximal colon, poorly differentiated, circumferential and mucinous tumours as well as increasing T stage and larger tumour size. Knockdown of MCC in HCT116 colon cancer cells caused a reduction in E-cadherin protein level, which is a hallmark of epithelial-mesenchymal transition in cancer, and consequently diminished the E-cadherin/β-catenin complex. MCC knockdown disrupted cell-cell adhesive strength and integrity in the dispase and transepithelial electrical resistance assays, enhanced hepatocyte growth factor-induced cell scatter and increased tumour cell invasiveness in an organotypic assay. The Src/Abl inhibitor dasatinib, a candidate anti-invasive drug, abrogated the invasive properties induced by MCC deficiency. Mechanistically, we establish that MCC interacts with the E-cadherin/β-catenin complex. These data provide a significant advance in the current understanding of cell-cell adhesion in colon cancer cells.

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http://hdl.handle.net/10453/161767