Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.

Radiation and cisplatin-based chemotherapy are major treatments for nasopharyngeal carcinoma (NPC). However, a major impediment for further improving the cure rate is the development of treatment resistance with an undetermined molecular mechanism in metastatic NPC cells. Our established, highly met...

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Autores principales:	Ying-Ying Liang, Ming-Yuan Chen, Yi-Jun Hua, Shi Chen, Li-Sheng Zheng, Xue Cao, Li-Xia Peng, Ping Xie, Bi-Jun Huang, Rui Sun, Lin Wang, Yan-Qun Xiang, Xiang Guo, Chao-Nan Qian
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d635cbb4724b41c48bf67394b75d1c23
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spelling	oai:doaj.org-article:d635cbb4724b41c48bf67394b75d1c232021-11-25T06:08:20ZDownregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.1932-620310.1371/journal.pone.0100843https://doaj.org/article/d635cbb4724b41c48bf67394b75d1c232014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25028967/?tool=EBIhttps://doaj.org/toc/1932-6203Radiation and cisplatin-based chemotherapy are major treatments for nasopharyngeal carcinoma (NPC). However, a major impediment for further improving the cure rate is the development of treatment resistance with an undetermined molecular mechanism in metastatic NPC cells. Our established, highly metastatic NPC cells have been reported to be more resistant to cisplatin chemotherapy. In the present study, we found that Ras association domain family member 6 (RASSF6) was downregulated in highly metastatic cells but upregulated in low metastatic cells in comparison to their parental cell line. Ectopic-expression of RASSF6 enhanced the sensitivity of highly metastatic NPC cells to cisplatin or radiation by enhancing apoptosis. RASSF6 depletion conversely reduced treatment sensitivity by decreasing the apoptosis rate. Over-expression of RASSF6 in highly metastatic NPC cells could enhance the phosphorylation of JNK when exposed to cisplatin or radiation treatment, while knocking down RASSF6 in low metastatic NPC cells could reduce the level of phospho-JNK when exposed to the same treatments. The activation of JNK signaling by RASSF6 and its subsequent sensitivity to apoptosis in NPC cells could be inhibited by applying the JNK inhibitor SP600125. In conclusion, the downregulation of RASSF6 in highly metastatic NPC cells contributed to their treatment resistance, and over-expression of RASSF6 conferred treatment sensitivity to highly metastatic NPC cells by activating JNK signaling. RASSF6 could be a valuable molecular marker for identifying sensitive metastatic NPC tumors during cisplatin treatment or radiotherapy.Ying-Ying LiangMing-Yuan ChenYi-Jun HuaShi ChenLi-Sheng ZhengXue CaoLi-Xia PengPing XieBi-Jun HuangRui SunLin WangYan-Qun XiangXiang GuoChao-Nan QianPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e100843 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying-Ying Liang Ming-Yuan Chen Yi-Jun Hua Shi Chen Li-Sheng Zheng Xue Cao Li-Xia Peng Ping Xie Bi-Jun Huang Rui Sun Lin Wang Yan-Qun Xiang Xiang Guo Chao-Nan Qian Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
description	Radiation and cisplatin-based chemotherapy are major treatments for nasopharyngeal carcinoma (NPC). However, a major impediment for further improving the cure rate is the development of treatment resistance with an undetermined molecular mechanism in metastatic NPC cells. Our established, highly metastatic NPC cells have been reported to be more resistant to cisplatin chemotherapy. In the present study, we found that Ras association domain family member 6 (RASSF6) was downregulated in highly metastatic cells but upregulated in low metastatic cells in comparison to their parental cell line. Ectopic-expression of RASSF6 enhanced the sensitivity of highly metastatic NPC cells to cisplatin or radiation by enhancing apoptosis. RASSF6 depletion conversely reduced treatment sensitivity by decreasing the apoptosis rate. Over-expression of RASSF6 in highly metastatic NPC cells could enhance the phosphorylation of JNK when exposed to cisplatin or radiation treatment, while knocking down RASSF6 in low metastatic NPC cells could reduce the level of phospho-JNK when exposed to the same treatments. The activation of JNK signaling by RASSF6 and its subsequent sensitivity to apoptosis in NPC cells could be inhibited by applying the JNK inhibitor SP600125. In conclusion, the downregulation of RASSF6 in highly metastatic NPC cells contributed to their treatment resistance, and over-expression of RASSF6 conferred treatment sensitivity to highly metastatic NPC cells by activating JNK signaling. RASSF6 could be a valuable molecular marker for identifying sensitive metastatic NPC tumors during cisplatin treatment or radiotherapy.
format	article
author	Ying-Ying Liang Ming-Yuan Chen Yi-Jun Hua Shi Chen Li-Sheng Zheng Xue Cao Li-Xia Peng Ping Xie Bi-Jun Huang Rui Sun Lin Wang Yan-Qun Xiang Xiang Guo Chao-Nan Qian
author_facet	Ying-Ying Liang Ming-Yuan Chen Yi-Jun Hua Shi Chen Li-Sheng Zheng Xue Cao Li-Xia Peng Ping Xie Bi-Jun Huang Rui Sun Lin Wang Yan-Qun Xiang Xiang Guo Chao-Nan Qian
author_sort	Ying-Ying Liang
title	Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
title_short	Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
title_full	Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
title_fullStr	Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
title_full_unstemmed	Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
title_sort	downregulation of ras association domain family member 6 (rassf6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d635cbb4724b41c48bf67394b75d1c23
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Downregulation of Ras association domain family member 6 (RASSF6) underlies the treatment resistance of highly metastatic nasopharyngeal carcinoma cells.

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