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YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy

Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor c...

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Autores principales: Chien, Chu-Yen, Chen, Ying-Chen, Hsu, Chia-Chen, Chou, Yu-Ting, Shiah, Shine-Gwo, Liu, Shyun-Yeu, Hsieh, Alexander Cheng-Ting, Yen, Ching-Yu, Lee, Chien-Hsing, Shieh, Yi-Shing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392082/
https://www.ncbi.nlm.nih.gov/pubmed/34440849
http://dx.doi.org/10.3390/cells10082080
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author Chien, Chu-Yen
Chen, Ying-Chen
Hsu, Chia-Chen
Chou, Yu-Ting
Shiah, Shine-Gwo
Liu, Shyun-Yeu
Hsieh, Alexander Cheng-Ting
Yen, Ching-Yu
Lee, Chien-Hsing
Shieh, Yi-Shing
author_facet Chien, Chu-Yen
Chen, Ying-Chen
Hsu, Chia-Chen
Chou, Yu-Ting
Shiah, Shine-Gwo
Liu, Shyun-Yeu
Hsieh, Alexander Cheng-Ting
Yen, Ching-Yu
Lee, Chien-Hsing
Shieh, Yi-Shing
author_sort Chien, Chu-Yen
collection PubMed
description Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial–mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer.
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spelling pubmed-83920822021-08-28 YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy Chien, Chu-Yen Chen, Ying-Chen Hsu, Chia-Chen Chou, Yu-Ting Shiah, Shine-Gwo Liu, Shyun-Yeu Hsieh, Alexander Cheng-Ting Yen, Ching-Yu Lee, Chien-Hsing Shieh, Yi-Shing Cells Article Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial–mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer. MDPI 2021-08-13 /pmc/articles/PMC8392082/ /pubmed/34440849 http://dx.doi.org/10.3390/cells10082080 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chien, Chu-Yen
Chen, Ying-Chen
Hsu, Chia-Chen
Chou, Yu-Ting
Shiah, Shine-Gwo
Liu, Shyun-Yeu
Hsieh, Alexander Cheng-Ting
Yen, Ching-Yu
Lee, Chien-Hsing
Shieh, Yi-Shing
YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
title YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
title_full YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
title_fullStr YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
title_full_unstemmed YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
title_short YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy
title_sort yap-dependent bip induction is involved in nicotine-mediated oral cancer malignancy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392082/
https://www.ncbi.nlm.nih.gov/pubmed/34440849
http://dx.doi.org/10.3390/cells10082080
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