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

• Published in: PloS one 2019-05, Vol.14 (5), p.e0216661-e0216661
• Main Authors: Park, Young-Jin, Kim, Jue Young, Lee, Doo Young, Zhang, Xianglan, Bazarsad, Shadavlonjid, Chung, Won-Yoon, Kim, Jin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Biology and Life Sciences; Biotechnology; Breast cancer; Cancer; Cancer cells; Cancer research; Carcinoma; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Care and treatment; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell cycle; Cell Line, Tumor; Cell Nucleus - metabolism; Dentistry; Development and progression; DNA-Binding Proteins - genetics; Drug development; Enzyme Induction; Enzymes; Epigenetics; ErbB Receptors - metabolism; Female; Fibroblasts; Gelatinase B; Gene Expression; Gene Knockdown Techniques; Genetic aspects; Glucose; Glucose - metabolism; Health aspects; Heterografts; Human papillomavirus; Humans; Infections; Invasiveness; Keratinocytes - metabolism; Keratinocytes - pathology; Keratinocytes - virology; Kinases; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Matrix metalloproteinases; Medical research; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolism; Metalloproteinase; Mice; Mice, Inbred BALB C; Middle Aged; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Novels; Nuclei (cytology); Oncogene Proteins, Viral - genetics; Oral cancer; Oral squamous cell carcinoma; Papillomavirus E7 Proteins - genetics; Pathology; Phosphorylation; Physical Sciences; Prognosis; Proteins; Proto-Oncogene Protein c-ets-1 - metabolism; Research and Analysis Methods; RNA, Messenger - genetics; RNA, Messenger - metabolism; Squamous cell carcinoma; Therapeutics; Thyroid Hormone-Binding Proteins; Thyroid Hormones - genetics; Thyroid Hormones - metabolism; Transcription factors; Transfection; Tumorigenicity
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216661

This study aimed at investigating the molecular mechanism underlying PKM2-mediated cancer invasion. 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. 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. Collectively, this study unveiled the molecular mechanism underlying PKM2-mediated cancer invasion, thereby providing novel targets for therapeutics development against invasive OSCC.