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PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer
Pyruvate kinase M2 (PKM2) is a key driver of aerobic glycolysis in cancer cells and has been shown to be up-regulated by mTOR in vitro. Our previous proteomic profiling studies showed that PKM2 was significantly upregulated in cervical cancer tissues after treatment with neoadjuvant chemotherapy (NA...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974606/ https://www.ncbi.nlm.nih.gov/pubmed/27492148 http://dx.doi.org/10.1038/srep30788 |
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author | Zhu, Haiyan Wu, Jun Zhang, Wenwen Luo, Hui Shen, Zhaojun Cheng, Huihui Zhu, Xueqiong |
author_facet | Zhu, Haiyan Wu, Jun Zhang, Wenwen Luo, Hui Shen, Zhaojun Cheng, Huihui Zhu, Xueqiong |
author_sort | Zhu, Haiyan |
collection | PubMed |
description | Pyruvate kinase M2 (PKM2) is a key driver of aerobic glycolysis in cancer cells and has been shown to be up-regulated by mTOR in vitro. Our previous proteomic profiling studies showed that PKM2 was significantly upregulated in cervical cancer tissues after treatment with neoadjuvant chemotherapy (NACT). Whether PKM2 expression predicts cisplatin-based NACT sensitivity and is mTOR dependent in cervical cancer patients remains unclear. Using paired tumor samples (pre- and post-chemotherapy) from 36 cervical cancer patients, we examined mTOR, HIF-1α, c-Myc, and PKM2 expression in cervical cancer samples and investigated the response to cisplatin-based NACT. In addition, we established PKM2 suppressed cervical cancer cell lines and evaluated their sensitivity to cisplatin in vitro. We found that the mTOR/HIF-1α/c-Myc/PKM2 signaling pathway was significantly downregulated in post-chemotherapy cervical cancer tissues. High levels of mTOR, HIF-1α, c-Myc, and PKM2 were associated with a positive chemotherapy response in cervical cancer patients treated with cisplatin-based NACT. In vitro, PKM2 knockdown desensitized cervical cancer cells to cisplatin. Moreover, PKM2 had complex interactions with mTOR pathways. mTOR, HIF1α, c-Myc, and PKM2 expression in cervical cancer may serve as predictive biomarkers to cisplatin-based chemotherapy. PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer. |
format | Online Article Text |
id | pubmed-4974606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49746062016-08-17 PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer Zhu, Haiyan Wu, Jun Zhang, Wenwen Luo, Hui Shen, Zhaojun Cheng, Huihui Zhu, Xueqiong Sci Rep Article Pyruvate kinase M2 (PKM2) is a key driver of aerobic glycolysis in cancer cells and has been shown to be up-regulated by mTOR in vitro. Our previous proteomic profiling studies showed that PKM2 was significantly upregulated in cervical cancer tissues after treatment with neoadjuvant chemotherapy (NACT). Whether PKM2 expression predicts cisplatin-based NACT sensitivity and is mTOR dependent in cervical cancer patients remains unclear. Using paired tumor samples (pre- and post-chemotherapy) from 36 cervical cancer patients, we examined mTOR, HIF-1α, c-Myc, and PKM2 expression in cervical cancer samples and investigated the response to cisplatin-based NACT. In addition, we established PKM2 suppressed cervical cancer cell lines and evaluated their sensitivity to cisplatin in vitro. We found that the mTOR/HIF-1α/c-Myc/PKM2 signaling pathway was significantly downregulated in post-chemotherapy cervical cancer tissues. High levels of mTOR, HIF-1α, c-Myc, and PKM2 were associated with a positive chemotherapy response in cervical cancer patients treated with cisplatin-based NACT. In vitro, PKM2 knockdown desensitized cervical cancer cells to cisplatin. Moreover, PKM2 had complex interactions with mTOR pathways. mTOR, HIF1α, c-Myc, and PKM2 expression in cervical cancer may serve as predictive biomarkers to cisplatin-based chemotherapy. PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer. Nature Publishing Group 2016-08-05 /pmc/articles/PMC4974606/ /pubmed/27492148 http://dx.doi.org/10.1038/srep30788 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhu, Haiyan Wu, Jun Zhang, Wenwen Luo, Hui Shen, Zhaojun Cheng, Huihui Zhu, Xueqiong PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer |
title | PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer |
title_full | PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer |
title_fullStr | PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer |
title_full_unstemmed | PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer |
title_short | PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer |
title_sort | pkm2 enhances chemosensitivity to cisplatin through interaction with the mtor pathway in cervical cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974606/ https://www.ncbi.nlm.nih.gov/pubmed/27492148 http://dx.doi.org/10.1038/srep30788 |
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