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Twist1 enhances hypoxia induced radioresistance in cervical cancer cells by promoting nuclear EGFR localization

Twist1 enhances hypoxia induced radioresistance in cervical cancer cells by promoting nuclear EGFR localization
Twist1 enhances hypoxia induced radioresistance in cervical cancer cells by promoting nuclear EGFR localization
Twist1 is a crucial transcription factor that regulates epithelial mesenchymal transition and involves in metastasis. Recent evidence suggests that Twist1 plays important role in hypoxia-induced radioresistance, but the underlying mechanism remains elusive. Here we investigated the change of Twist1 expression in human cervical squamous cancer cell line SiHa after hypoxia treatment. We also explored the role of Twist1 in radioresistance by manipulating the expression level of Twist1.

We observed that hypoxia treatment elevated the expression of Twist1 in SiHa cells. Knockdown of Twist1 with siRNA increased the radiosensitivity of SiHa cells under hypoxia condition, accompanied by reduced levels of nuclear Epidermal Growth Factor Receptor (EGFR) and DNA-dependent protein kinase (DNA-PK). Conversely, overexpression of Twist1 led to increased radioresistance of SiHa cells, which in turn increased nuclear EGFR localisation and expression levels of nuclear DNA-PK. Moreover, concomitant high expression of hypoxia-inducible factor-1? (HIF-1?) and Twist1 in primary tumors of cervical cancer patients correlated with the worse prognosis after irradiation treatment. Taken together, these data provide new insights into molecular mechanism underlying hypoxia-induced radio resistance in cervical cancer cells, and suggest that Twist1 is a promising molecular target to improve the efficacy of cancer radiotherapy.
345-353
Xiong, Hua
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Nie, Xin
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Zou, Yanmei
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Gong, Chen
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Li, Yang
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Wu, Hua
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Qiu, Hong
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Yang, Lin
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Zhuang, Liang
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Zhang, Peng
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Zhang, Jing
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Wang, Yihua
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Xiong, Huihua
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Xiong, Hua
f80e5b10-9793-40ae-8143-1762577028f4
Nie, Xin
1dda13d2-cb39-46f8-ac20-9a0a904c6dd6
Zou, Yanmei
6783820d-2ff0-4900-9ade-34fe1180f56f
Gong, Chen
9c82ac6c-0541-4ba5-8941-19ec6fdd0898
Li, Yang
7b845265-9eab-4e0a-a6ba-61bdba4a6968
Wu, Hua
f66bf993-3474-4e4d-a82e-aa61dff9f6de
Qiu, Hong
dc13a95d-9523-43de-94c3-ddd4ff9809aa
Yang, Lin
6aeb13ea-a392-418e-9161-3e4ea899c89c
Zhuang, Liang
0203bc0f-51f3-4924-b526-6ffebadff4a5
Zhang, Peng
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Zhang, Jing
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Wang, Yihua
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Xiong, Huihua
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Xiong, Hua, Nie, Xin, Zou, Yanmei, Gong, Chen, Li, Yang, Wu, Hua, Qiu, Hong, Yang, Lin, Zhuang, Liang, Zhang, Peng, Zhang, Jing, Wang, Yihua and Xiong, Huihua (2017) Twist1 enhances hypoxia induced radioresistance in cervical cancer cells by promoting nuclear EGFR localization. Journal of Cancer, 8 (3), 345-353. (doi:10.7150/jca.16607).

Record type: Article

Abstract

Twist1 is a crucial transcription factor that regulates epithelial mesenchymal transition and involves in metastasis. Recent evidence suggests that Twist1 plays important role in hypoxia-induced radioresistance, but the underlying mechanism remains elusive. Here we investigated the change of Twist1 expression in human cervical squamous cancer cell line SiHa after hypoxia treatment. We also explored the role of Twist1 in radioresistance by manipulating the expression level of Twist1.

We observed that hypoxia treatment elevated the expression of Twist1 in SiHa cells. Knockdown of Twist1 with siRNA increased the radiosensitivity of SiHa cells under hypoxia condition, accompanied by reduced levels of nuclear Epidermal Growth Factor Receptor (EGFR) and DNA-dependent protein kinase (DNA-PK). Conversely, overexpression of Twist1 led to increased radioresistance of SiHa cells, which in turn increased nuclear EGFR localisation and expression levels of nuclear DNA-PK. Moreover, concomitant high expression of hypoxia-inducible factor-1? (HIF-1?) and Twist1 in primary tumors of cervical cancer patients correlated with the worse prognosis after irradiation treatment. Taken together, these data provide new insights into molecular mechanism underlying hypoxia-induced radio resistance in cervical cancer cells, and suggest that Twist1 is a promising molecular target to improve the efficacy of cancer radiotherapy.

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Accepted/In Press date: 29 October 2016
Published date: 9 February 2017
Organisations: Biomedicine

Identifiers

Local EPrints ID: 405661
URI: http://eprints.soton.ac.uk/id/eprint/405661
PURE UUID: 59b88982-8d2c-40fa-996a-3cfc878ea280
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

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Date deposited: 10 Feb 2017 11:41
Last modified: 16 Mar 2024 04:22

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Contributors

Author: Hua Xiong
Author: Xin Nie
Author: Yanmei Zou
Author: Chen Gong
Author: Yang Li
Author: Hua Wu
Author: Hong Qiu
Author: Lin Yang
Author: Liang Zhuang
Author: Peng Zhang
Author: Jing Zhang
Author: Yihua Wang ORCID iD
Author: Huihua Xiong

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