ESM-1 regulates cell growth and metastatic process through activation of NF-kB in colorectal cancer

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Title
ESM-1 regulates cell growth and metastatic process through activation of NF-kB in colorectal cancer
Author(s)
Yun Hee Kang; N Y Ji; S R Han; C I Lee; Jae Wha KimYoung Il Yeom; Y H Kim; H K Chun; J W Kim; J W Chung; D K Ahn; Hee Gu Lee; Eun Young Song
Bibliographic Citation
Cellular Signalling, vol. 24, no. 10, pp. 1940-1949
Publication Year
2012
Abstract
In our previous study, we reported that endothelial cell specific molecule-1 (ESM-1) was increased in tissue and serum from colorectal cancer patients and suggested that ESM-1 can be used as a potential serum marker for early detection of colorectal cancer. The aim of this study was to evaluate the role of ESM-1 as an intracellular molecule in colorectal cancer. ESM-1 expression was knocked down by small interfering RNA (siRNA) in colorectal cancer cells. Expression of ESM-1 siRNA decreased cell survival through the Akt-dependent inhibition of NF-κB/IκB pathway and an interconnected reduction in phospho-Akt, -p38, -ERK1, -RSK1, -GSK-3α/β and -HSP27, as determined by a phospho-MAPK array. ESM-1 silencing induced G 1 phase cell cycle arrest by induction of PTEN, resulting in the inhibition of cyclin D1 and inhibited cell migration and invasion of COLO205 cells. Consistently, ESM-1 overexpression in HCT-116 cells enhanced cell proliferation through the Akt-dependent activation of NF-κB pathway. In addition, ESM-1 interacted with NF-κB and activated NF-κB promoter. This study demonstrates that ESM-1 is involved in cell survival, cell cycle progression, migration, invasion and EMT during tumor invasion in colorectal cancer. Based on our results, ESM-1 may be a useful therapeutic target for colorectal cancer.
Keyword
Cell growthColorectal cancerESM-1Metastatic processNF-κB activation
ISSN
0898-6568
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.cellsig.2012.06.004
Type
Article
Appears in Collections:
Division of Biomaterials Research > Cell Factory Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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