TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

Sabrina Daniela da Silva, Moulay A Alaoui-Jamali, Fernando Augusto Soares, Dirce Maria Carraro, Helena Paula Brentani, Michael Hier, Silvia Regina Rogatto, Luiz Paulo Kowalski

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.

METHODS: The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.

RESULTS: Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.

CONCLUSIONS: The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC.

OriginalsprogEngelsk
TidsskriftCancer
Vol/bind120
Udgave nummer3
Sider (fra-til)352-62
Antal sider11
ISSN0008-543X
DOI
StatusUdgivet - 1. feb. 2014
Udgivet eksterntJa

Fingeraftryk

Twist-Related Protein 1
Mouth Neoplasms
Up-Regulation
Oral Stage
Reverse Transcriptase Polymerase Chain Reaction
Lymph Nodes

Citer dette

da Silva, S. D., Alaoui-Jamali, M. A., Soares, F. A., Carraro, D. M., Brentani, H. P., Hier, M., ... Kowalski, L. P. (2014). TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target. Cancer, 120(3), 352-62. https://doi.org/10.1002/cncr.28404
da Silva, Sabrina Daniela ; Alaoui-Jamali, Moulay A ; Soares, Fernando Augusto ; Carraro, Dirce Maria ; Brentani, Helena Paula ; Hier, Michael ; Rogatto, Silvia Regina ; Kowalski, Luiz Paulo. / TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target. I: Cancer. 2014 ; Bind 120, Nr. 3. s. 352-62.
@article{31840c34c5a341ca80d7e9e6db963854,
title = "TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target",
abstract = "BACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.METHODS: The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.RESULTS: Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.CONCLUSIONS: The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC.",
keywords = "Animals, Carcinoma, Squamous Cell, Cells, Cultured, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Humans, Male, Mice, Mouth Neoplasms, Nuclear Proteins, Prognosis, Twist Transcription Factor",
author = "{da Silva}, {Sabrina Daniela} and Alaoui-Jamali, {Moulay A} and Soares, {Fernando Augusto} and Carraro, {Dirce Maria} and Brentani, {Helena Paula} and Michael Hier and Rogatto, {Silvia Regina} and Kowalski, {Luiz Paulo}",
note = "{\circledC} 2013 American Cancer Society.",
year = "2014",
month = "2",
day = "1",
doi = "10.1002/cncr.28404",
language = "English",
volume = "120",
pages = "352--62",
journal = "Cancer",
issn = "0008-543X",
publisher = "JohnWiley & Sons, Inc.",
number = "3",

}

da Silva, SD, Alaoui-Jamali, MA, Soares, FA, Carraro, DM, Brentani, HP, Hier, M, Rogatto, SR & Kowalski, LP 2014, 'TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target', Cancer, bind 120, nr. 3, s. 352-62. https://doi.org/10.1002/cncr.28404

TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target. / da Silva, Sabrina Daniela; Alaoui-Jamali, Moulay A; Soares, Fernando Augusto; Carraro, Dirce Maria; Brentani, Helena Paula; Hier, Michael; Rogatto, Silvia Regina; Kowalski, Luiz Paulo.

I: Cancer, Bind 120, Nr. 3, 01.02.2014, s. 352-62.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target

AU - da Silva, Sabrina Daniela

AU - Alaoui-Jamali, Moulay A

AU - Soares, Fernando Augusto

AU - Carraro, Dirce Maria

AU - Brentani, Helena Paula

AU - Hier, Michael

AU - Rogatto, Silvia Regina

AU - Kowalski, Luiz Paulo

N1 - © 2013 American Cancer Society.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - BACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.METHODS: The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.RESULTS: Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.CONCLUSIONS: The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC.

AB - BACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.METHODS: The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.RESULTS: Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.CONCLUSIONS: The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC.

KW - Animals

KW - Carcinoma, Squamous Cell

KW - Cells, Cultured

KW - Epithelial-Mesenchymal Transition

KW - Female

KW - Gene Expression Profiling

KW - Humans

KW - Male

KW - Mice

KW - Mouth Neoplasms

KW - Nuclear Proteins

KW - Prognosis

KW - Twist Transcription Factor

U2 - 10.1002/cncr.28404

DO - 10.1002/cncr.28404

M3 - Journal article

VL - 120

SP - 352

EP - 362

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 3

ER -

da Silva SD, Alaoui-Jamali MA, Soares FA, Carraro DM, Brentani HP, Hier M et al. TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target. Cancer. 2014 feb 1;120(3):352-62. https://doi.org/10.1002/cncr.28404