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NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis

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NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis. / Salameti, Vasiliki; Bhosale, Priyanka G; Ames-Draycott, Ashley; Sipilä, Kalle; Watt, Fiona M.

In: Oncotarget, Vol. 10, No. 63, 26.11.2019, p. 6791-6804.

Research output: Contribution to journalArticle

Harvard

Salameti, V, Bhosale, PG, Ames-Draycott, A, Sipilä, K & Watt, FM 2019, 'NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis', Oncotarget, vol. 10, no. 63, pp. 6791-6804. https://doi.org/10.18632/oncotarget.27306

APA

Salameti, V., Bhosale, P. G., Ames-Draycott, A., Sipilä, K., & Watt, F. M. (2019). NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis. Oncotarget, 10(63), 6791-6804. https://doi.org/10.18632/oncotarget.27306

Vancouver

Salameti V, Bhosale PG, Ames-Draycott A, Sipilä K, Watt FM. NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis. Oncotarget. 2019 Nov 26;10(63):6791-6804. https://doi.org/10.18632/oncotarget.27306

Author

Salameti, Vasiliki ; Bhosale, Priyanka G ; Ames-Draycott, Ashley ; Sipilä, Kalle ; Watt, Fiona M. / NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis. In: Oncotarget. 2019 ; Vol. 10, No. 63. pp. 6791-6804.

Bibtex Download

@article{7acc1469a81047a98b108f6f6d99bc4e,
title = "NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis",
abstract = "Inactivating mutations in the EGF-like ligand binding domain of NOTCH1 are a prominent feature of the mutational landscape of oral squamous cell carcinoma (OSCC). In this study, we investigated NOTCH1 mutations in keratinocyte lines derived from OSCC biopsies that had been subjected to whole exome sequencing. One line, SJG6, was found to have truncating mutations in both NOTCH1 alleles, resulting in loss of NOTCH1 expression. Overexpression of the NOTCH1 intracellular domain (NICD) in SJG6 cells promoted cell adhesion and differentiation, while suppressing proliferation, migration and clonal growth, consistent with the previously reported tumour suppressive function of NOTCH1 in OSCC. Comparative gene expression profiling identified SERPINE1 as being downregulated on NICD overexpression and predicted an interaction between SERPINE1 and genes involved in cell proliferation and migration. Mechanistically, overexpression of NICD resulted in upregulation of ETV7/TEL2, which negatively regulates SERPINE1 expression. Knockdown of SERPINE1 phenocopied the effects of NICD overexpression in culture. Consistent with previous studies and our in vitro findings, there were inverse correlations between ETV7 and SERPINE1 expression and survival in OSCC primary tumours. Our results suggest that the tumour suppressive role of NOTCH1 in OSCC is mediated, at least in part, by inhibition of SERPINE1 via ETV7.",
keywords = "Cell adhesion, ETV7/TEL2, NOTCH1, Oral squamous cell carcinoma (OSCC), SERPINE1",
author = "Vasiliki Salameti and Bhosale, {Priyanka G} and Ashley Ames-Draycott and Kalle Sipil{\"a} and Watt, {Fiona M}",
year = "2019",
month = nov,
day = "26",
doi = "10.18632/oncotarget.27306",
language = "English",
volume = "10",
pages = "6791--6804",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "63",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis

AU - Salameti, Vasiliki

AU - Bhosale, Priyanka G

AU - Ames-Draycott, Ashley

AU - Sipilä, Kalle

AU - Watt, Fiona M

PY - 2019/11/26

Y1 - 2019/11/26

N2 - Inactivating mutations in the EGF-like ligand binding domain of NOTCH1 are a prominent feature of the mutational landscape of oral squamous cell carcinoma (OSCC). In this study, we investigated NOTCH1 mutations in keratinocyte lines derived from OSCC biopsies that had been subjected to whole exome sequencing. One line, SJG6, was found to have truncating mutations in both NOTCH1 alleles, resulting in loss of NOTCH1 expression. Overexpression of the NOTCH1 intracellular domain (NICD) in SJG6 cells promoted cell adhesion and differentiation, while suppressing proliferation, migration and clonal growth, consistent with the previously reported tumour suppressive function of NOTCH1 in OSCC. Comparative gene expression profiling identified SERPINE1 as being downregulated on NICD overexpression and predicted an interaction between SERPINE1 and genes involved in cell proliferation and migration. Mechanistically, overexpression of NICD resulted in upregulation of ETV7/TEL2, which negatively regulates SERPINE1 expression. Knockdown of SERPINE1 phenocopied the effects of NICD overexpression in culture. Consistent with previous studies and our in vitro findings, there were inverse correlations between ETV7 and SERPINE1 expression and survival in OSCC primary tumours. Our results suggest that the tumour suppressive role of NOTCH1 in OSCC is mediated, at least in part, by inhibition of SERPINE1 via ETV7.

AB - Inactivating mutations in the EGF-like ligand binding domain of NOTCH1 are a prominent feature of the mutational landscape of oral squamous cell carcinoma (OSCC). In this study, we investigated NOTCH1 mutations in keratinocyte lines derived from OSCC biopsies that had been subjected to whole exome sequencing. One line, SJG6, was found to have truncating mutations in both NOTCH1 alleles, resulting in loss of NOTCH1 expression. Overexpression of the NOTCH1 intracellular domain (NICD) in SJG6 cells promoted cell adhesion and differentiation, while suppressing proliferation, migration and clonal growth, consistent with the previously reported tumour suppressive function of NOTCH1 in OSCC. Comparative gene expression profiling identified SERPINE1 as being downregulated on NICD overexpression and predicted an interaction between SERPINE1 and genes involved in cell proliferation and migration. Mechanistically, overexpression of NICD resulted in upregulation of ETV7/TEL2, which negatively regulates SERPINE1 expression. Knockdown of SERPINE1 phenocopied the effects of NICD overexpression in culture. Consistent with previous studies and our in vitro findings, there were inverse correlations between ETV7 and SERPINE1 expression and survival in OSCC primary tumours. Our results suggest that the tumour suppressive role of NOTCH1 in OSCC is mediated, at least in part, by inhibition of SERPINE1 via ETV7.

KW - Cell adhesion

KW - ETV7/TEL2

KW - NOTCH1

KW - Oral squamous cell carcinoma (OSCC)

KW - SERPINE1

UR - http://www.scopus.com/inward/record.url?scp=85075592957&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.27306

DO - 10.18632/oncotarget.27306

M3 - Article

C2 - 31827722

AN - SCOPUS:85075592957

VL - 10

SP - 6791

EP - 6804

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 63

ER -

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