L1-CAM knock-down radiosensitizes neuroblastoma IMR-32 cells by simultaneously decreasing MycN, but increasing PTEN protein expression

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dc.contributor.author Rached, Johnny
dc.contributor.author Nasr, Zeina
dc.contributor.author Abdallah, Jad
dc.contributor.author Abou-Antoun, Tamara
dc.date.accessioned 2017-12-18T09:44:32Z
dc.date.available 2017-12-18T09:44:32Z
dc.date.copyright 2016 en_US
dc.date.issued 2017-12-18
dc.identifier.issn 1791-2423 en_US
dc.identifier.uri http://hdl.handle.net/10725/6821
dc.description.abstract Childhood neuroblastoma is one of the most malignant types of cancers leading to a high mortality rate. These cancerous cells can be highly metastatic and malignant giving rise to disease recurrence and poor prognosis. The proto-oncogene myelocytomatosis neuroblastoma (MycN) is known to be amplified in this type of cancer, thus, promoting high malignancy and resistance. The L1 cell adhesion molecule (L1-CAM) cleavage has been found upregulated in many types of malignant cancers. In the present study, we explored the interplay between L1-CAM, MycN and PTEN as well as the role played by PDGFR and VEGFR on tumorigenicity in neuroblastoma cells. We investigated the effect of L1-CAM knock-down (KD) and PDGFR/VEGFR inhibition with sunitinib malate (Sutent®) treatment on subsequent tumorsphere formation and cellular proliferation and migration in the MycN-amplified IMR-32 neuroblastoma cells. We further examined the effect of combined L1-CAM KD with Sutent treatment or radiotherapy on these cellular functions in our cells. Tumorsphere formation is one of the indicators of aggressiveness in malignant cancers, which was significantly inhibited in IMR-32 cells after L1-CAM KD or Sutent treatment, however, no synergistic effect was observed with dual treatments, rather L1-CAM KD alone showed a greater inhibition on tumorsphere formation compared to Sutent treatment alone. In addition, cellular proliferation and migration were significantly inhibited after L1-CAM KD in the IMR-32 cells with no synergistic effect observed on the rate of cell proliferation when combined with Sutent treatment. Again, L1-CAM KD alone exhibited greater inhibitory effect than Sutent treatment on cell proliferation. L1-CAM KD led to the simultaneous downregulation of MycN, but the upregulation of PTEN protein expression. Notably, radiotherapy (2 Gy) of the IMR-32 cells led to significant upregulation of both L1-CAM and MycN, which was abrogated with L1-CAM KD in our cells. In addition, L1-CAM KD radiosensitized the cells as exhibited by the synergistic effect on the reduction in cell proliferation compared to radiotherapy alone. Taken together, our data show the importance of L1-CAM interplay with MycN and PTEN on the MycN amplified neuroblastoma cell radioresistance, proliferation and motility. en_US
dc.language.iso en en_US
dc.title L1-CAM knock-down radiosensitizes neuroblastoma IMR-32 cells by simultaneously decreasing MycN, but increasing PTEN protein expression en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOP en_US
dc.author.idnumber 200703820 en_US
dc.author.idnumber 201005279
dc.author.department Pharmaceutical Sciences Department en_US
dc.description.embargo N/A en_US
dc.relation.journal International Journal of Oncology en_US
dc.journal.volume 49 en_US
dc.journal.issue 4 en_US
dc.article.pages 1722-1730 en_US
dc.identifier.doi https://doi.org/10.3892/ijo.2016.3625 en_US
dc.identifier.ctation Rached, J., Nasr, Z., Abdallah, J., & Abou-Antoun, T. (2016). L1-CAM knock-down radiosensitizes neuroblastoma IMR-32 cells by simultaneously decreasing MycN, but increasing PTEN protein expression. International journal of oncology, 49(4), 1722-1730. en_US
dc.author.email jabdallah@lau.edu.lb en_US
dc.author.email tamara.abouantoun@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.spandidos-publications.com/ijo/49/4/1722 en_US
dc.orcid.id https://orcid.org/0000-0001-5267-4953 en_US
dc.author.affiliation Lebanese American University en_US
dc.orcid.id2 https://orcid.org/0000-0003-2898-0779 en_US

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