Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression

  • Authors:
    • Kaiyan Liu
    • Zhenjie Tang
    • Amin Huang
    • Ping Chen
    • Panpan Liu
    • Jing Yang
    • Wenhua Lu
    • Jianwei Liao
    • Yicheng Sun
    • Shijun Wen
    • Yumin Hu
    • Peng Huang
  • View Affiliations

  • Published online on: November 18, 2016     https://doi.org/10.3892/ijo.2016.3774
  • Pages: 252-262
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Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in multiple cellular functions including metabolism and gene transcription. Our previous study showed that GAPDH expression was elevated in colon cancer and further upregulated in liver metastatic tissues, suggesting a possilbe role of GAPDH in promoting cancer metastasis. The present study was designed to investigate the underlying mechanism, using multiple experimental approaches including genetic silencing of GAPDH expression by short hairpin RNA (shRNA) and biochemcial/molecular analyses of the key events involved in glycolytic metabolism and epithelial-mesenchymal transition (EMT). We showed that silencing of GAPDH expression resulted in a significant reduction of glycolysis in colon cancer cell lines, accompanied by a decrease in cell proliferation and an apparent change in cell morphology associated with alterations in actin expression and phalloidine staining patterns. Furthermore, GAPDH suppression also caused a downregulation of gene expression involved in cancer stem-like cells and EMT. CHIP assay and co-immunoprecipitation revealed that GAPDH physically interacted with the transcriptional factor Sp1 and enhance the expression of SNAIL, a major regulator of EMT. Suppression of GAPDH expression resulted in a signficant decrease in SNAIL expression, leading to inhibition of EMT and attenuation of colon cancer cell migration in vitro and reduced metastasis in vivo. Overall, the present study suggests that GAPDH plays an important role in cancer metastasis by affecting EMT through regulation of Sp1-mediated SNAIL expression.
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January-2017
Volume 50 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu K, Tang Z, Huang A, Chen P, Liu P, Yang J, Lu W, Liao J, Sun Y, Wen S, Wen S, et al: Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression. Int J Oncol 50: 252-262, 2017
APA
Liu, K., Tang, Z., Huang, A., Chen, P., Liu, P., Yang, J. ... Huang, P. (2017). Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression. International Journal of Oncology, 50, 252-262. https://doi.org/10.3892/ijo.2016.3774
MLA
Liu, K., Tang, Z., Huang, A., Chen, P., Liu, P., Yang, J., Lu, W., Liao, J., Sun, Y., Wen, S., Hu, Y., Huang, P."Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression". International Journal of Oncology 50.1 (2017): 252-262.
Chicago
Liu, K., Tang, Z., Huang, A., Chen, P., Liu, P., Yang, J., Lu, W., Liao, J., Sun, Y., Wen, S., Hu, Y., Huang, P."Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression". International Journal of Oncology 50, no. 1 (2017): 252-262. https://doi.org/10.3892/ijo.2016.3774