Publication: Gadd45β silencing impaired viability and metastatic phenotypesin cholangiocarcinoma cells by modulating the emt pathway
Issued Date
2018-03-01
Resource Type
ISSN
17921082
17921074
17921074
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2-s2.0-85040809997
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Mahidol University
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SCOPUS
Bibliographic Citation
Oncology Letters. Vol.15, No.3 (2018), 3031-3041
Suggested Citation
Kyaw Zwar Myint, Pornparn Kongpracha, Panthip Rattanasinganchan, Kawin Leelawat, Penpak Moolthiya, Kittipong Chaiyabutr, Rutaiwan Tohtong Gadd45β silencing impaired viability and metastatic phenotypesin cholangiocarcinoma cells by modulating the emt pathway. Oncology Letters. Vol.15, No.3 (2018), 3031-3041. doi:10.3892/ol.2017.7706 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45225
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Title
Gadd45β silencing impaired viability and metastatic phenotypesin cholangiocarcinoma cells by modulating the emt pathway
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Abstract
© 2018, Spandidos Publications. All rights reserved. Growth arrest and DNA damage-inducible-ß (Gadd45ß) is a stress-response protein involved in a number of processes, including cell cycle control, DNA repair, survival and death control, and stress signaling, depending on its interactions. Gadd45ß expression is dysregulated in numerous types of cancer, functioning as either a tumor promoter or a tumor suppressor. However, the functions of Gadd45ß in cholangiocarcinoma (CCA), particularly in metastasis, has not been studied. The immunohistochemical analysis of Gadd45ß expression revealed that 75% of histological specimens from patients with CCA expressed high levels of Gadd45ß, and that high Gadd45ß expression was associated with metastasis. The role of Gadd45ß in CCA was examined using siRNA-mediated gene knockdown in HuCCA-1, a human CCA cell line established from a Thai patient. The effects of Gadd45ß downregulation upon cell viability and death, invasion, migration, matrix metalloproteinase (MMP) activity and epithelial-mesenchymal transition (EMT) marker expression were investigated. Gadd45ß knockdown impaired cell viability, which was associated with the induction of apoptosis. In addition, there was a marked reduction in invasion and migration, although MMP activity was unaffected. Impairment of these metastatic properties was accompanied by the decreased expression of EMT markers, including Slug, vimentin, claudin-1 and zona occludens protein 1, whereas E-cadherin expression was increased. The present study suggests that Gadd45ß is involved in regulating the viability and the metastatic potential of CCA cells, which may be mediated by the modulation of the EMT pathway.