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PKM2 enhances cancer invasion via ETS-1-dependent 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 
 PLoS One, Vol.14(5) : e0216661, 2019 
Journal Title
 PLoS One 
Issue Date
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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Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ju Young(김주영)
Kim, Jin(김진)
Park, Young Jin(박영진)
Zhang, Xiang Lan(장향란)
Chung, Won Yoon(정원윤) ORCID logo https://orcid.org/0000-0001-8428-9005
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