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FEBS Lett. 2014 Aug 25;588(17):3240-50. doi: 10.1016/j.febslet.2014.07.006. Epub 2014 Jul 11.

Nitric oxide increases the invasion of pancreatic cancer cells via activation of the PI3K-AKT and RhoA pathways after carbon ion irradiation.

Author information

1
Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
2
Research Center Hospital, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
3
Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan. Electronic address: imait@nirs.go.jp.

Abstract

Previous studies have shown that serine proteases and Rho-associated kinase contribute to carbon ion radiation-enhanced invasion of the human pancreatic cancer cell line PANC-1. The results presented here show that nitric oxide synthase (NOS) also plays a critical role in this process. Irradiation of PANC-1 cells promoted invasion and production of nitric oxide (NO), which activated the PI3K-AKT signaling pathway, while independently activating RhoA. Inhibition of PI3K, Rho-associated kinase, and serine protease alone or in conjunction with NOS suppressed the radiation-enhanced invasion of PANC-1 cells, suggesting that they could serve as possible targets for the management of tumor metastasis.

KEYWORDS:

Invasion; Nitric oxide synthase; Phosphatidylinositol 3-kinase; Plasminogen activator; Rho; v-akt murine thymoma viral oncogene homolog 2

PMID:
25019574
DOI:
10.1016/j.febslet.2014.07.006
[Indexed for MEDLINE]
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