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
- Park, Jong Kuk; Park, Seon Ho; So, Kwangsup; Bae, In Hwa; Yoo, Young Do; Um, Hong-Duck
- Issue Date
- 1월-2010
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- ICAM-3; migration; invasion; Akt; CREB; MMP
- Citation
- INTERNATIONAL JOURNAL OF ONCOLOGY, v.36, no.1, pp.181 - 192
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF ONCOLOGY
- Volume
- 36
- Number
- 1
- Start Page
- 181
- End Page
- 192
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/117270
- DOI
- 10.3892/ijo_00000489
- ISSN
- 1019-6439
- Abstract
- We have previously reported that intercellular adhesion molecule-3 (ICAM-3) is associated with ail 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 its 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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