PKM2 enhances cancer invasion via ETS-1dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells

Young Jin Park; Jue Young Kim; Doo Young Lee; Xianglan Zhang; Shadavlonjid Bazarsad; Won Yoon Chung; Jin Kim

doi:10.1371/journal.pone.0216661

PKM2 enhances cancer invasion via ETS-1dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells

Young Jin Park, Jue Young Kim, Doo Young Lee, Xianglan Zhang, Shadavlonjid Bazarsad, Won Yoon Chung, Jin Kim

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Objectives This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion. Materials & methods To optimize the investigation of PKM2-specific effects, we used two immortalized oral cell lines. The two cell lines drastically differed in PKM2 expression level, particularly in the level of nuclear PKM2, and subsequently in glucose metabolism and tumorigenicity. Results Knockdown of PKM2 reduced not only the glucose metabolism but also the invasive activity by curtailing the expressions of matrix metalloproteinases (MMP): PKM2 could modulate MMP-9 expression by regulating ETS-1 inside the nucleus. These results were further confirmed in an oral squamous cell carcinoma (OSCC) cell line. In correspondence with in vitro findings, clinicopathological data from OSCC patients indicated strong association between PKM2 expression and poor survival rate. Additionally, upon analysis of public database, significant positive correlation was found between PKM2 and ETS-1 in OSCC. Conclusion Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC.

Original language	English
Article number	e0216661
Journal	PloS one
Volume	14
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0216661
Publication status	Published - 2019 May

Bibliographical note

Funding Information:
This work was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0094027 to JK) and by the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare (HI15C1901 to WYC), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2019 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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title = "PKM2 enhances cancer invasion via ETS-1dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells",

abstract = "Objectives This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion. Materials & methods To optimize the investigation of PKM2-specific effects, we used two immortalized oral cell lines. The two cell lines drastically differed in PKM2 expression level, particularly in the level of nuclear PKM2, and subsequently in glucose metabolism and tumorigenicity. Results Knockdown of PKM2 reduced not only the glucose metabolism but also the invasive activity by curtailing the expressions of matrix metalloproteinases (MMP): PKM2 could modulate MMP-9 expression by regulating ETS-1 inside the nucleus. These results were further confirmed in an oral squamous cell carcinoma (OSCC) cell line. In correspondence with in vitro findings, clinicopathological data from OSCC patients indicated strong association between PKM2 expression and poor survival rate. Additionally, upon analysis of public database, significant positive correlation was found between PKM2 and ETS-1 in OSCC. Conclusion Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC.",

author = "Park, {Young Jin} and Kim, {Jue Young} and Lee, {Doo Young} and Xianglan Zhang and Shadavlonjid Bazarsad and Chung, {Won Yoon} and Jin Kim",

note = "Funding Information: This work was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0094027 to JK) and by the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare (HI15C1901 to WYC), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2019 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Park, Young Jin

AU - Kim, Jue Young

AU - Lee, Doo Young

AU - Zhang, Xianglan

AU - Bazarsad, Shadavlonjid

AU - Chung, Won Yoon

AU - Kim, Jin

N1 - Funding Information: This work was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0094027 to JK) and by the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare (HI15C1901 to WYC), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2019 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2019/5

Y1 - 2019/5

N2 - Objectives This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion. Materials & methods To optimize the investigation of PKM2-specific effects, we used two immortalized oral cell lines. The two cell lines drastically differed in PKM2 expression level, particularly in the level of nuclear PKM2, and subsequently in glucose metabolism and tumorigenicity. Results Knockdown of PKM2 reduced not only the glucose metabolism but also the invasive activity by curtailing the expressions of matrix metalloproteinases (MMP): PKM2 could modulate MMP-9 expression by regulating ETS-1 inside the nucleus. These results were further confirmed in an oral squamous cell carcinoma (OSCC) cell line. In correspondence with in vitro findings, clinicopathological data from OSCC patients indicated strong association between PKM2 expression and poor survival rate. Additionally, upon analysis of public database, significant positive correlation was found between PKM2 and ETS-1 in OSCC. Conclusion Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC.

AB - Objectives This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion. Materials & methods To optimize the investigation of PKM2-specific effects, we used two immortalized oral cell lines. The two cell lines drastically differed in PKM2 expression level, particularly in the level of nuclear PKM2, and subsequently in glucose metabolism and tumorigenicity. Results Knockdown of PKM2 reduced not only the glucose metabolism but also the invasive activity by curtailing the expressions of matrix metalloproteinases (MMP): PKM2 could modulate MMP-9 expression by regulating ETS-1 inside the nucleus. These results were further confirmed in an oral squamous cell carcinoma (OSCC) cell line. In correspondence with in vitro findings, clinicopathological data from OSCC patients indicated strong association between PKM2 expression and poor survival rate. Additionally, upon analysis of public database, significant positive correlation was found between PKM2 and ETS-1 in OSCC. Conclusion Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC.

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PKM2 enhances cancer invasion via ETS-1dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells

Abstract

Bibliographical note

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UN SDGs

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