Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer

Pen Yuan Chu, Fang Wei Hu, Cheng Chia Yu, Lo Lin Tsai, Chuan Hang Yu, Buor Chang Wu, Yi Wei Chen, Pin I. Huang, Wen Liang Lo

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Objectives: Both epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties may be involved in metastasis, which contributes to the high mortality rate of patients with head and neck cancers (HNCs). However, the mechanisms through which the EMT transcription factors ZEB1 and ZEB2 regulate HNC are still unclear. Methods: Tumor initiating capability of HNC-CH133 + cells with ZEB1/2 knockdown or co-overexpression was presented in vitro and in vivo. Results: In the present study, we demonstrated that ZEB1/ZEB2 expression was significantly increased in HNC-CD133+ CSC-like cells compared with HNC-CD133- cells. The small interfering RNA (siRNA)-mediated co-knockdown of ZEB1 and ZEB2 (siZEB1/2) in HNC-CH133 + cells suppressed their CSC-like properties, including self-renewal ability, the expression of stemness markers, and drug resistance. In contrast, the co-overexpression of ZEB1/ZEB2 in HNC-CD133- cells enhanced their sphere-forming ability and increased the percentage of CD44-positive cells and side population cells. In vivo studies showed that the delivery of siZEB1/2 to xenograft tumors in nude mice reduced tumor growth and the rate of distant metastasis. In clinical samples, the levels of ZEB1/ZEB2 expression were low in local lesions but high in metastatic lymph nodes in HNC tissues. Patients with tumors that co-expressed ZEB1high and ZEB2high had especially poor survival rates. Conclusion: Therapies targeting ZEB1/ZEB2 in HNC-CD133+ cells may provide a new approach for HNC therapy in the future.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalOral Oncology
Volume49
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Head and Neck Neoplasms
Transcription Factors
Neoplasms
Neoplastic Stem Cells
Side-Population Cells
Neoplasm Metastasis
Mesenchymal Stromal Cells
Drug Resistance
Heterografts
Nude Mice
Small Interfering RNA
Survival Rate
Lymph Nodes

Keywords

  • Cancer stem cells
  • EMT
  • Head and neck cancer
  • ZEB1
  • ZEB2

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer. / Chu, Pen Yuan; Hu, Fang Wei; Yu, Cheng Chia; Tsai, Lo Lin; Yu, Chuan Hang; Wu, Buor Chang; Chen, Yi Wei; Huang, Pin I.; Lo, Wen Liang.

In: Oral Oncology, Vol. 49, No. 1, 01.2013, p. 34-41.

Research output: Contribution to journalArticle

Chu, Pen Yuan ; Hu, Fang Wei ; Yu, Cheng Chia ; Tsai, Lo Lin ; Yu, Chuan Hang ; Wu, Buor Chang ; Chen, Yi Wei ; Huang, Pin I. ; Lo, Wen Liang. / Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer. In: Oral Oncology. 2013 ; Vol. 49, No. 1. pp. 34-41.
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abstract = "Objectives: Both epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties may be involved in metastasis, which contributes to the high mortality rate of patients with head and neck cancers (HNCs). However, the mechanisms through which the EMT transcription factors ZEB1 and ZEB2 regulate HNC are still unclear. Methods: Tumor initiating capability of HNC-CH133 + cells with ZEB1/2 knockdown or co-overexpression was presented in vitro and in vivo. Results: In the present study, we demonstrated that ZEB1/ZEB2 expression was significantly increased in HNC-CD133+ CSC-like cells compared with HNC-CD133- cells. The small interfering RNA (siRNA)-mediated co-knockdown of ZEB1 and ZEB2 (siZEB1/2) in HNC-CH133 + cells suppressed their CSC-like properties, including self-renewal ability, the expression of stemness markers, and drug resistance. In contrast, the co-overexpression of ZEB1/ZEB2 in HNC-CD133- cells enhanced their sphere-forming ability and increased the percentage of CD44-positive cells and side population cells. In vivo studies showed that the delivery of siZEB1/2 to xenograft tumors in nude mice reduced tumor growth and the rate of distant metastasis. In clinical samples, the levels of ZEB1/ZEB2 expression were low in local lesions but high in metastatic lymph nodes in HNC tissues. Patients with tumors that co-expressed ZEB1high and ZEB2high had especially poor survival rates. Conclusion: Therapies targeting ZEB1/ZEB2 in HNC-CD133+ cells may provide a new approach for HNC therapy in the future.",
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AU - Tsai, Lo Lin

AU - Yu, Chuan Hang

AU - Wu, Buor Chang

AU - Chen, Yi Wei

AU - Huang, Pin I.

AU - Lo, Wen Liang

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AB - Objectives: Both epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties may be involved in metastasis, which contributes to the high mortality rate of patients with head and neck cancers (HNCs). However, the mechanisms through which the EMT transcription factors ZEB1 and ZEB2 regulate HNC are still unclear. Methods: Tumor initiating capability of HNC-CH133 + cells with ZEB1/2 knockdown or co-overexpression was presented in vitro and in vivo. Results: In the present study, we demonstrated that ZEB1/ZEB2 expression was significantly increased in HNC-CD133+ CSC-like cells compared with HNC-CD133- cells. The small interfering RNA (siRNA)-mediated co-knockdown of ZEB1 and ZEB2 (siZEB1/2) in HNC-CH133 + cells suppressed their CSC-like properties, including self-renewal ability, the expression of stemness markers, and drug resistance. In contrast, the co-overexpression of ZEB1/ZEB2 in HNC-CD133- cells enhanced their sphere-forming ability and increased the percentage of CD44-positive cells and side population cells. In vivo studies showed that the delivery of siZEB1/2 to xenograft tumors in nude mice reduced tumor growth and the rate of distant metastasis. In clinical samples, the levels of ZEB1/ZEB2 expression were low in local lesions but high in metastatic lymph nodes in HNC tissues. Patients with tumors that co-expressed ZEB1high and ZEB2high had especially poor survival rates. Conclusion: Therapies targeting ZEB1/ZEB2 in HNC-CD133+ cells may provide a new approach for HNC therapy in the future.

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