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, WonYoon Chung, Jin Kim

Research output: Contribution to journalArticle

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 languageEnglish
Article numbere0216661
JournalPloS one
Volume14
Issue number5
DOIs
Publication statusPublished - 2019 May 1

Fingerprint

squamous cell carcinoma
metalloproteinases
Matrix Metalloproteinases
Squamous Cell Carcinoma
mouth
Cells
neoplasms
Metabolism
Cell Line
cell lines
Neoplasms
cells
Glucose
Matrix Metalloproteinase 9
glucose
gelatinase B
metabolism
Survival Rate
Databases
survival rate

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Park, Young Jin ; Kim, Jue Young ; Lee, Doo Young ; Zhang, Xianglan ; Bazarsad, Shadavlonjid ; Chung, WonYoon ; Kim, Jin. / PKM2 enhances cancer invasion via ETS-1dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells. In: PloS one. 2019 ; Vol. 14, No. 5.
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PKM2 enhances cancer invasion via ETS-1dependent induction of matrix metalloproteinase in oral squamous cell carcinoma cells. / Park, Young Jin; Kim, Jue Young; Lee, Doo Young; Zhang, Xianglan; Bazarsad, Shadavlonjid; Chung, WonYoon; Kim, Jin.

In: PloS one, Vol. 14, No. 5, e0216661, 01.05.2019.

Research output: Contribution to journalArticle

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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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