ESM-1 regulates cell growth and metastatic process through activation of NF-κB in colorectal cancer.
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.
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Yun Hee
YH
Kang
Na Young
NY
Ji
Seung Ro
SR
Han
Chung Il
CI
Lee
Jae Wha
JW
Kim
Young Il
YI
Yeom
Young Ho
YH
Kim
Ho Kyung
HK
Chun
Jong Wan
JW
Kim
Jin Woong
JW
Chung
Dong Kuk
DK
Ahn
Hee Gu
HG
Lee
Eun Young
EY
Song
D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D019938:Cyclin D1 / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D051059:PTEN Phosphohydrolase / Q000276:immunology; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
C101134:ESM1 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D020782:Matrix Metalloproteinases