ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB

  • Authors:
    • Jong Kuk Park
    • Seon Ho Park
    • Kwangsup So
    • In Hwa Bae
    • Young Do Yoo
    • Hong-Duck Um
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/ijo_00000489
  • Pages: 181-192
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Abstract

We have previously reported that intercellular adhesion molecule-3 (ICAM-3) is associated with an increase of cellular radio-resistance and cancer cell proliferation. In this study, we hypothesized that ICAM-3 has an additional effect on cancer cell migration and invasion because molecules induced by ICAM-3 are known as regulators of cell migration and invasion. To examine this hypothesis, we used NCI-H1299 non-small cell lung cancer (NSCLC) cell line (p53 and PTEN null cell) and constructed an ICAM-3-over-expressing stable transfectant, which exhibited increased cell migration and invasion. The increased migration and invasion resulted from up-regulation of expression and activities of MMP-2 and MMP-9. ICAM-3 also increased Akt phosphorylation, which caused an increase in cellular migration/invasion and MMP activities. Activity of several transcriptional factors located downstream in the Akt pathway was also tested, and constitutive activation of adenosine 3', 5'-monophosphate response element-binding protein (CREB) by ICAM-3 was detected. Blockage of the Akt pathway attenuated CREB activation, and a decrease in CREB expression reduced cellular migration/invasion and activity of MMPs. This result indicates that CREB functions in the signaling pathway between Akt and MMP. We also showed ICAM-3-induced cell migration and invasion in NCI-H460 NSCLC cells (wild-type p53 and PTEN cell) through the same signaling pathway. Taken together, our findings suggest that ICAM-3 stimulates cancer cell migration/invasion via ICAM-3/Akt/CREB/MMP pathway regardless of p53 and PTEN status, and this reflects the possibility that ICAM-3 could be considered as a candidate for anti-cancer drug development and as a cancer diagnostic marker.

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January 2010
Volume 36 Issue 1

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

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APA
Park, J.K., Park, S.H., So, K., Bae, I.H., Yoo, Y.D., & Um, H. (2010). ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB. International Journal of Oncology, 36, 181-192. https://doi.org/10.3892/ijo_00000489
MLA
Park, J. K., Park, S. H., So, K., Bae, I. H., Yoo, Y. D., Um, H."ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB". International Journal of Oncology 36.1 (2010): 181-192.
Chicago
Park, J. K., Park, S. H., So, K., Bae, I. H., Yoo, Y. D., Um, H."ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB". International Journal of Oncology 36, no. 1 (2010): 181-192. https://doi.org/10.3892/ijo_00000489